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Tobón-Cornejo S, Sanchez-Tapia M, Guizar-Heredia R, Velázquez Villegas L, Noriega LG, Furuzawa-Carballeda J, Hernández-Pando R, Vázquez-Manjarrez N, Granados-Portillo O, López-Barradas A, Rebollar-Vega R, Maya O, Miller AW, Serralde A, Guevara-Cruz M, Torres N, Tovar AR. Increased dietary protein stimulates amino acid catabolism via the gut microbiota and secondary bile acid production. Gut Microbes 2025; 17:2465896. [PMID: 39980327 DOI: 10.1080/19490976.2025.2465896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 12/27/2024] [Accepted: 02/05/2025] [Indexed: 02/22/2025] Open
Abstract
Excess amino acids from a protein-rich diet are mainly catabolized in the liver. However, it is still unclear to what extent the gut microbiota may be involved in the mechanisms governing this catabolism. Therefore, the aim of this study was to investigate whether consumption of different dietary protein concentrations induces changes in the taxonomy of the gut microbiota, which may contribute to the regulation of hepatic amino acid catabolism. Consumption of a high-protein diet caused overexpression of HIF-1α in the colon and increase in mitochondrial activity, creating a more anaerobic environment that was associated with changes in the taxonomy of the gut microbiota promoting an increase in the synthesis of secondary bile acids, increased secretion of pancreatic glucagon. This effect was demonstrated in pancreatic islets, where secondary bile acids stimulated the expression of the PC2 enzyme that promotes glucagon formation. The increase in circulating glucagon was associated with an induction of the expression of hepatic amino acid-degrading enzymes, an effect attenuated by antibiotics. Thus, high protein intake in mice and humans induced the increase of different species in the gut microbiota with the capacity to produce secondary bile acids leading to an increase in secondary bile acids and glucagon levels, promoting amino acid catabolism.
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Affiliation(s)
- Sandra Tobón-Cornejo
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Monica Sanchez-Tapia
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Rocio Guizar-Heredia
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Laura Velázquez Villegas
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Lilia G Noriega
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Janette Furuzawa-Carballeda
- Departamento de Cirugía Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Rogelio Hernández-Pando
- Departamento de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Natalia Vázquez-Manjarrez
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Omar Granados-Portillo
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Adriana López-Barradas
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Rosa Rebollar-Vega
- RED de apoyo a la investigación, Coordinación de la Investrigación Científica, UNAM e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Otoniel Maya
- Physics Department, Chalmers University of Technology, Chalmers E-Commons, Gothenburg, Sweden
| | - Aaron W Miller
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Aurora Serralde
- Departamento de Nutrición Clínica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Martha Guevara-Cruz
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Nimbe Torres
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Armando R Tovar
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
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Ferreira MDR, Scalzo MDLM, Rodríguez S, D Alessandro ME. Changes in cerebral cortex redox status and cognitive performance in short- and long-term high-sucrose diet fed rats. Physiol Behav 2025; 290:114776. [PMID: 39638221 DOI: 10.1016/j.physbeh.2024.114776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 11/14/2024] [Accepted: 12/02/2024] [Indexed: 12/07/2024]
Abstract
Rising evidence suggests that Metabolic Syndrome (MetS) would be correlated with the development of neurodegenerative diseases. Although this has emerged as a relevant area of research, it has not been fully explored. It is not clear if a greater impairment of the metabolic peripheral environment is accompanied by a greater impairment of the central nervous system. We have previously shown that feeding rats with a high-sucrose diet (HSD) represents an animal model that resembles the human MetS phenotype. The aim of the present work was to assess in rats fed a HSD for a short (3 weeks-wk) or a long (15 weeks-wk) term, whether the worsening of the peripheral metabolic and hormonal profile that occur as the time of HSD consumption increases, is also accompanied by a worsening of oxidative stress in the cerebral cortex and/or cognitive behavior. Male Wistar rats received a HSD or a control diet during 3 wk or 15 wk. We found an increase in reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), advanced glycation end products (AGEs) and glutathione peroxidase (GPx) and glutathione reductase (GR) enzyme activities in the cerebral cortex of 3 wk HSD-fed rats. All of these parameters, except for the GPx, were also increased in the 15 wk HSD-fed group and values were similar to those observed at 3 wk. Glutathione reduced form (GSH), catalase (CAT) activity and brain-to-body weight ratio were reduced in 15 wk HSD-fed animals. Glutathione S- transferase (GST) was similar in all dietary groups. A poor performance in novel object recognition test and T-maze memory tasks was observed in 3 wk and 15 wk HSD-fed rats in a similar magnitude. Our results add new evidence related to the association between an adverse peripheral metabolic environment and brain/cognitive dysfunction.
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Affiliation(s)
- María Del Rosario Ferreira
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral. Ciudad Universitaria, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
| | - María de Los Milagros Scalzo
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral. Ciudad Universitaria, Santa Fe, Argentina
| | - Silvia Rodríguez
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - María Eugenia D Alessandro
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral. Ciudad Universitaria, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
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3
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Bartlett A, Blakeley-Ruiz JA, Richie T, Theriot CM, Kleiner M. Large Quantities of Bacterial DNA and Protein in Common Dietary Protein Source Used in Microbiome Studies. Proteomics 2025:e202400149. [PMID: 39981802 DOI: 10.1002/pmic.202400149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 02/05/2025] [Accepted: 02/06/2025] [Indexed: 02/22/2025]
Abstract
Diet has been shown to greatly impact the intestinal microbiota. To understand the role of individual dietary components, defined diets with purified components are frequently used in diet-microbiota studies. Defined diets frequently use purified casein as the protein source. Previous work indicated that casein contains microbial DNA potentially impacting results of microbiome studies. Other diet-based microbially derived molecules that may impact microbiome measurements, such as proteins detected by metaproteomics, have not been determined for casein. Additionally, other protein sources used in microbiome studies have not been characterized for their microbial content. We used metagenomics and metaproteomics to identify and quantify microbial DNA and protein in a casein-based defined diet to better understand potential impacts on metagenomic and metaproteomic microbiome studies. We further tested six additional defined diets with purified protein sources with an integrated metagenomic-metaproteomic approach and found that contaminating microbial protein is unique to casein within the tested set as microbial protein was not identified in diets with other protein sources. We also illustrate the contribution of diet-derived microbial protein in diet-microbiota studies by metaproteomic analysis of stool samples from germ-free mice (GF) and mice with a conventional microbiota (CV) following consumption of diets with casein and non-casein protein. This study highlights a potentially confounding factor in diet-microbiota studies that must be considered through evaluation of the diet itself within a given study.
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Affiliation(s)
- Alexandria Bartlett
- Department of Plant and Microbial Biology, North Carolina State University, Raleigh, North Carolina, USA
- Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA
| | - J Alfredo Blakeley-Ruiz
- Department of Plant and Microbial Biology, North Carolina State University, Raleigh, North Carolina, USA
| | - Tanner Richie
- Department of Plant and Microbial Biology, North Carolina State University, Raleigh, North Carolina, USA
| | - Casey M Theriot
- Department of Population Health and Pathobiology, North Carolina State University, Raleigh, North Carolina, USA
| | - Manuel Kleiner
- Department of Plant and Microbial Biology, North Carolina State University, Raleigh, North Carolina, USA
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Soma H, Yoshida R, Ishizuka S. Quantitative analysis of sterol balance in a mouse model of hepatic lipid accumulation induced by cholesterol and cholic acid supplementation. Biosci Biotechnol Biochem 2025; 89:438-445. [PMID: 39656874 DOI: 10.1093/bbb/zbae183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 11/27/2024] [Indexed: 12/17/2024]
Abstract
The cholesterol balance and bile acid metabolism in a mouse model of hepatic lipid accumulation induced by a diet supplemented with cholesterol and cholic acid (CA) were quantitatively evaluated. The mice were fed diets supplemented with different levels of cholesterol (0, 3, or 6 g/kg of diet) and CA (0.5 g/kg of diet) for 6 weeks. Cholesterol supplementation doubled the hepatic triglyceride concentration, regardless of the supplementation level, without inflammation or gallstone formation. Both cholesterol supplementations enhanced fecal excretion of muricholic acid. Additionally, the higher cholesterol supplementation led to an increase in fecal cholesterol excretion, accompanied by elevated expression of hepatic cholesterol exporters and a reduction in fecal bile acid excretion. In this mouse study, supplementation with 3 g cholesterol/kg diet and 0.5 g CA/kg diet was sufficient to induce hepatic lipid accumulation.
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Affiliation(s)
- Hinata Soma
- Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan
| | - Ryo Yoshida
- Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan
| | - Satoshi Ishizuka
- Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan
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Kij A, Kieronska-Rudek A, Bar A, Czyzynska-Cichon I, Strus M, Kozien L, Wiecek G, Zeber-Lubecka N, Kulecka M, Kwiatkowski G, Przyborowski K, Mohaissen T, Sternak M, Buczek E, Zakrzewska A, Proniewski B, Kus K, Franczyk-Zarow M, Kostogrys RB, Pieterman EJ, Princen HMG, Chlopicki S. Low phylloquinone intake deteriorates endothelial function in normolipidemic and dyslipidaemic mice. J Nutr Biochem 2025:109867. [PMID: 39978646 DOI: 10.1016/j.jnutbio.2025.109867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 01/10/2025] [Accepted: 02/13/2025] [Indexed: 02/22/2025]
Abstract
While the plasma phylloquinone (PK) concentration is inversely correlated with cardiovascular risk, the involvement of PK in regulating endothelial function has not been directly investigated. Therefore, in this study we assessed the effects of short-term treatment with PK-deficient diets (5-10 weeks) on endothelial function in normolipidemic 14-week-old male C57BL/6JCmd mice and age-matched dyslipidaemic male E3L.CETP mice. Our results show that in normolipidemic mice dietary PK deficiency was associated with a marked reduction of PK levels in the plasma and liver (liquid chromatography-mass spectrometry measurements) and with impaired endothelium-dependent vasodilation assessed in vivo by magnetic resonance imaging (MRI). Dietary PK deficiency-induced endothelial dysfunction was fully reversed by PK supplementation. In dyslipidaemic E3L.CETP mice, dietary PK deficiency exacerbated preexisting endothelial dysfunction. Furthermore, dietary PK deficiency decreased menaquinone-4 (MK-4) levels in the aorta but did not affect blood coagulation (calibrated automated thrombography), microbiota composition (culturing and next-generation sequencing), and gut menaquinone production. In conclusion, our study demonstrated for the first time that sufficient dietary PK intake supports endothelial function in normolipidemic and dyslipidaemic mice indicating nutritional significance of dietary PK in the maintenance of endothelial function in humans.
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Affiliation(s)
- Agnieszka Kij
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Anna Kieronska-Rudek
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland; Jagiellonian University Medical College, Chair of Pharmacology, Grzegorzecka 16, 31-531 Krakow, Poland
| | - Anna Bar
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Izabela Czyzynska-Cichon
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Magdalena Strus
- Jagiellonian University Medical College, Department of Bacteriology, Microbial Ecology and Parasitology, Chair of Microbiology, Czysta 18, 31-121 Krakow, Poland
| | - Lucja Kozien
- Jagiellonian University Medical College, Department of Bacteriology, Microbial Ecology and Parasitology, Chair of Microbiology, Czysta 18, 31-121 Krakow, Poland
| | - Grazyna Wiecek
- Jagiellonian University Medical College, Department of Bacteriology, Microbial Ecology and Parasitology, Chair of Microbiology, Czysta 18, 31-121 Krakow, Poland
| | - Natalia Zeber-Lubecka
- Centre of Postgraduate Medical Education Department of Gastroenterology, Hepatology and Clinical Oncology, Roentgena 5, 02-781 Warszawa, Poland; Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781 Warszawa, Poland
| | - Maria Kulecka
- Centre of Postgraduate Medical Education Department of Gastroenterology, Hepatology and Clinical Oncology, Roentgena 5, 02-781 Warszawa, Poland; Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781 Warszawa, Poland
| | - Grzegorz Kwiatkowski
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Kamil Przyborowski
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Tasnim Mohaissen
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Magdalena Sternak
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Elzbieta Buczek
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Agnieszka Zakrzewska
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Bartosz Proniewski
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Kamil Kus
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland
| | - Magdalena Franczyk-Zarow
- University of Agriculture in Krakow, Faculty of Food Technology, Department of Human Nutrition and Dietetics, Mickiewicza 21, 31-120 Krakow, Poland
| | - Renata B Kostogrys
- University of Agriculture in Krakow, Faculty of Food Technology, Department of Human Nutrition and Dietetics, Mickiewicza 21, 31-120 Krakow, Poland
| | - Elsbeth J Pieterman
- The Netherlands Organization of Applied Scientific Research (TNO), Metabolic Health Research, Gaubius Laboratory, 2333BE Leiden, The Netherlands
| | - Hans M G Princen
- The Netherlands Organization of Applied Scientific Research (TNO), Metabolic Health Research, Gaubius Laboratory, 2333BE Leiden, The Netherlands
| | - Stefan Chlopicki
- Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland; Jagiellonian University Medical College, Chair of Pharmacology, Grzegorzecka 16, 31-531 Krakow, Poland.
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Dos Santos AAA, Torrezan R, Rodrigues WDNDS, Ribeiro MVG, Ferreira ARO, Peres MNC, Saavedra LPJ, Raposo SR, Almeida DL, Malta A, Mathias PCDF. High-fat diet during lactation, as opposed to during adolescence or gestation, programs cardiometabolic and autonomic dysfunctions in adult offspring. Brain Res 2025; 1849:149354. [PMID: 39603318 DOI: 10.1016/j.brainres.2024.149354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 09/06/2024] [Accepted: 11/24/2024] [Indexed: 11/29/2024]
Abstract
The Developmental Origins of Health and Disease (DOHaD) concept has been established for three decades. Many studies have shown that, besides pregnancy, other plastic phases (mainly preconception, lactation, and infancy-adolescence) are also sensitive to environmental changes, including nutritional conditions, that can program health or disease later in life. This study compared the susceptibility of the gestation, lactation and adolescence to a high-fat diet (HFD) intervention to program rats into autonomic nervous system imbalance and cardiometabolic dysfunction in adulthood. Four groups of rats were studied: offspring from mothers exposed to a HFD (35% fat) or a standard chow diet (4.5% fat) during gestation (GEST and CONT groups, respectively), offspring from mothers exposed to the HFD during lactation (LAC), and adolescent rats exposed to the HFD (ADOL). Mothers treated during pregnancy exhibited a higher body mass, but nursing mothers presented the highest food energy intake and higher adiposity. Compared to the other groups, the LAC rats showed increased body mass gain, food energy intake, body fat, glucose intolerance and blood pressure. LAC group also showed increased parasympathetic activity. In contrast, LAC sympathetic nerve activity decreased compared with the other groups. The ADOL group exhibited mostly similar responses but of a smaller magnitude. This suggests that the lactation phase is the most sensitive to HFD programming for cardiometabolic dysfunction in adulthood and that early overnutrition may affect neural connections by altering the autonomic nervous system balance.
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Affiliation(s)
- Annie Araújo Alves Dos Santos
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Rosana Torrezan
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | | | - Maiara Vanusa Guedes Ribeiro
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Anna Rebeka Oliveira Ferreira
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Maria Natália Chimirri Peres
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Lucas Paulo Jacinto Saavedra
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Scarlett Rodrigues Raposo
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Douglas Lopes Almeida
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Ananda Malta
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil.
| | - Paulo Cezar de Freitas Mathias
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
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Vasconcelos de Araújo AN, Gomes Dutra LM, Dantas BS, Alves AF, Almeida Gonçalves SA, Tribuzy de Magalhães Cordeiro AM, Barbosa Soares JK, de Souza Aquino J. Impact of preconceptional intermittent fasting on reflex ontogenesis, physical and somatic development of the offspring of Wistar rats. Brain Res 2025:149510. [PMID: 39956379 DOI: 10.1016/j.brainres.2025.149510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 01/14/2025] [Accepted: 02/13/2025] [Indexed: 02/18/2025]
Abstract
BACKGROUND Intermittent fasting (IF) has health benefits; however, little is known about its effects on the offspring when practiced by dams in the preconception period. The aim of the study was to evaluate the impact of IF during the preconception period on physical and somatic parameters, as well as on the reflex ontogenesis of Wistar rat offspring. METHODS The female rats were randomized into two groups: control (CG) and intermittent fasting group (IF) submitted to a feed restriction of 16 h for four weeks during the preconception period. Reproductive performance, body weight, and energy intake were evaluated in dams. Reflex ontogeny, physical and somatic development, brain fatty acids and the brain histology were evaluated in the offspring. RESULTS IF did not change the reproductive performance or weight of dams during the preconception period. An acceleration of vibrissae placing and negative geotaxis parameters of reflex ontogenesis was observed, as well as anticipation of the following physical development indicators: ear unfolding, an eruption of upper incisor teeth, and inferior teeth in the IF offspring. Although the nervous tissue did not present histological changes, the content of some brain fatty acids was found in greater amounts in the IF offspring such as dihomo-γ-linolenic acid (0.66 ± 0.01 %) and eicotrienoic acid (0.58 ± 0.03 %). CONCLUSION IF during preconception did not change the body weight or reproductive performance of the dams, and promoted beneficial effects on the neurodevelopment of the offspring in the early life.
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Affiliation(s)
- Alana Natalícia Vasconcelos de Araújo
- Laboratory of Experimental Nutrition, Department of Nutrition, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil; Post Gradutate Program of Nutrition Sciences, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil
| | - Larissa Maria Gomes Dutra
- Post Graduate Program of Food Science and Technology, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil; Laboratory of Experimental Nutrition, Department of Nutrition, Federal University of Campina Grande (UFCG), Cuité, PB, Brazil
| | - Bruno Silva Dantas
- Post Graduate Program of Food Science and Technology, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil; Laboratory of Experimental Nutrition, Department of Nutrition, Federal University of Campina Grande (UFCG), Cuité, PB, Brazil
| | - Adriano Francisco Alves
- Laboratory of General Pathology, Department of Physiology and Pathology, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil
| | | | | | - Juliana Késsia Barbosa Soares
- Post Graduate Program of Food Science and Technology, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil; Laboratory of Experimental Nutrition, Department of Nutrition, Federal University of Campina Grande (UFCG), Cuité, PB, Brazil
| | - Jailane de Souza Aquino
- Laboratory of Experimental Nutrition, Department of Nutrition, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil; Post Gradutate Program of Nutrition Sciences, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil; Post Graduate Program of Food Science and Technology, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil.
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Saini N, Mooney SM, Smith SM. Alcohol reprograms placental glucose and lipid metabolism which correlate with reduced fetal brain but not body weight in a mouse model of prenatal alcohol exposure. J Nutr 2025:S0022-3166(25)00091-4. [PMID: 39956392 DOI: 10.1016/j.tjnut.2025.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 02/04/2025] [Accepted: 02/06/2025] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND Prenatal alcohol exposure (PAE) impairs fetal growth and brain development. Dysregulated placental function contributes to these deficits. Whether PAE also disrupts its metabolic functions to impede fetal development is unclear. OBJECTIVES We performed untargeted metabolomics to gain mechanistic insights on how PAE impacts placental metabolism and fetal nutrient availability. METHODS Pregnant C57BL/6J mice were gavaged with alcohol (ALC, 3 g/kg) or isocaloric maltodextrin (CON) daily on embryonic days (E) E8.5 through E17.5. We performed untargeted metabolomics on placentas harvested at E17.5. RESULTS Alcohol reduced placental glucose and glycolytic intermediates and increased TCA cycle intermediates, suggesting a shift from glucose to lipids to meet its high energetic demands. This was complemented by elevations in intermediates of the pentose phosphate and glucosamine pathways, indicating a diversion of glucose into non-oxidative fates. Alcohol also decreased aspartate and asparagine, consistent with the limited glucose availability and increased fetal demand for nitrogen acceptors to support its increased gluconeogenesis and urea production. Alcohol also caused a selective increase in purine metabolites despite the limited availability of donor sources glucose, serine, glycine, glutamine, and asparagine. Uridine nucleotides were also elevated and may represent an adaptive change to meet the increased need for thiamin pyrophosphate in the oxidative decarboxylations of the TCA cycle and pentose phosphate pathways. Decreases in multiple oxylipins having anti-vasoconstriction actions could be a mechanism by which alcohol alters the placental vasculature and promotes vasoconstriction. Importantly, the selective and strong correlation of these dysregulated metabolites with reduced fetal brain weight, but not body weight, affirms the importance of the placenta-brain axis and placental metabolism on brain development. CONCLUSIONS Alcohol causes metabolic dysregulation and reprogramming of the late-term placenta. These changes limit fetal nutrient availability and contribute to the reduced brain development and cognitive impairments that partly typify PAE.
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Affiliation(s)
- Nipun Saini
- Nutrition Research Institute and Department of Nutrition, University of North Carolina at Chapel Hill.
| | - Sandra M Mooney
- Nutrition Research Institute and Department of Nutrition, University of North Carolina at Chapel Hill
| | - Susan M Smith
- Nutrition Research Institute and Department of Nutrition, University of North Carolina at Chapel Hill
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Liu X, Pang S, Song G, Wang Y, Fang W, Qi W. The alleviation by wheat and oat dietary fiber alone or combined of T2DM symptoms in db/ db mice. Food Funct 2025; 16:1142-1156. [PMID: 39835833 DOI: 10.1039/d4fo04037f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
The effects of wheat and oat dietary fiber (DF) alone or combined on T2DM remain unclear. In this research, db/db diabetic mice were fed with diets containing 10% insoluble wheat dietary fiber (WDF), 10% insoluble oat dietary fiber (ODF), and 10% WODF (mixture of WDF and ODF, WDF : ODF = 1 : 1) for 8 weeks. The results showed that WDF, ODF, and WODF all reduced the body weight and fasting blood glucose (FBG) and improved oral glucose tolerance in db/db mice. WDF and ODF alone further relieved insulin resistance and decreased the levels of glycated hemoglobin A1c (GHbA1c), and glycosylated serum protein (GSP). In addition, WDF and ODF alone decreased the levels of TNF-α, IL-6, and IL-1β in serum. The colon function was improved and similar changes were observed in the gut microbiota structure and abundance in all the DF groups. The change of gut microbiota mainly manifested as reducing F/B ratio at the phylum level, while at the genus level as decreasing Enterococcus, Escherichia-Shigella, Erysipelatoclostridium, and unclassified_f_Lachnospiraceae and increase of norank_f_Muribaculaceae, Bacteroides, and Alistipes. Further testing of colonic bile acids (BAs) revealed that WDF, ODF, and WODF all significantly changed the composition of BAs, mainly reducing the levels of UDCA, HDCA, and 3β-UDCA. WODF further decreased DCA and increased β-MCA, LCA-3S, and 12-KCDCA. Importantly, WODF reduced the values of 12-OH-BAs/non-12-OH-BAs. Moreover, the TGR5 level was up-regulated in both the liver and colon, and the FXR level was up-regulated in the liver while down-regulated in the colon in all the DF groups. Furthermore, for the protein level, IRS-1, p-PI3K/PI3K, and AKT were up-regulated in the liver in all the DF groups, while for the mRNA expression level, GLUT4 was up-regulated, and FOXO1, GSK3β, PEPCK, and PGC-1α were down-regulated. WDF and WODF further up-regulated the mRNA expression levels of GYS and down-regulated that of G6Pase. These results suggested that WDF, ODF, and WODF all can alleviate T2DM through the gutmicrobiota-BAs-TGR5/FXR axis and liver IRS-1/PI3K/AKT pathway in db/db mice. WDF and ODF alone are beneficial for improving glucose metabolism and inflammation indicators, while WODF helps improve BAs' profile more in the colon.
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Affiliation(s)
- Xinguo Liu
- Academy of National Food and Strategic Reserves Administration, Beijing, China.
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Shaojie Pang
- Heilongjiang Feihe Dairy Co., Ltd, C-16, 10A Jiuxianqiao Rd., Chaoyang, Beijing, China
| | - Ge Song
- Academy of National Food and Strategic Reserves Administration, Beijing, China.
| | - Yong Wang
- Academy of National Food and Strategic Reserves Administration, Beijing, China.
| | - Wei Fang
- Academy of National Food and Strategic Reserves Administration, Beijing, China.
| | - Wentao Qi
- Academy of National Food and Strategic Reserves Administration, Beijing, China.
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
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10
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Nandy A, Helderman RCM, Thapa S, Peck SH, Richards A, Jayapalan S, Narayani N, Czech MP, Rosen CJ, Rendina-Ruedy E. Enhanced fatty acid oxidation in osteoprogenitor cells provides protection from high-fat diet induced bone dysfunction. J Bone Miner Res 2025; 40:283-298. [PMID: 39657629 PMCID: PMC11789392 DOI: 10.1093/jbmr/zjae195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 11/14/2024] [Accepted: 12/04/2024] [Indexed: 12/12/2024]
Abstract
Bone homeostasis within the skeletal system is predominantly maintained by bone formation and resorption, where formation of new bone involves maturation of stromal cells to mineral and matrix secreting mature osteoblasts, which requires cellular energy or adenosine triphosphate. Alterations in systemic metabolism can influence osteoblast function. In line with this, type 2 diabetes mellitus (T2DM), a common metabolic disorder is also associated with reduced bone formation and increased risk of fracture. Impairment in lipid metabolism is one of the key features associated with T2DM-related pathologies in multiple tissues. Therefore, we tested the hypothesis that the reduced bone formation reported in obese murine models of impaired glucose tolerance is a function of disrupted lipid metabolism in osteoblasts. We first confirmed that mice fed a high-fat diet (HFD) have reduced bone microarchitecture along with lower bone formation rates. Interestingly, osteoblasts from obese mice harbor higher numbers of cytosolic lipid droplets along with decreased bioenergetic profiles compared to control cells. Further supporting this observation, bone cortex demonstrated higher total lipid content in HFD fed mice compared to control-fed mice. As a further proof of principle, we generated a novel murine model to conditionally delete Plin2 in osteoblast-progenitor cells using Prrx1-Cre, to enhance lipid droplet breakdown. Our data demonstrate that knocking down Plin2 in an osteoprogenitor specific manner protects from HFD induced osteoblast dysfunction. Furthermore, the mechanism of action involves enhanced osteoblast fatty acid oxidation. In conclusion, the current studies establish that HFD induced glucose intolerance leads to perturbations in osteoblast lipid metabolism, thus causing lower bone formation, which can be protected against by increasing fatty acid oxidation.
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Affiliation(s)
- Ananya Nandy
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - Ron C M Helderman
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
- Frank H. Netter M.D. School of Medicine, Quinnipiac University, North Haven, CT 06518, United States
| | - Santosh Thapa
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - Sun H Peck
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
- Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, United States
- Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN 37232, United States
- Department of Veterans Affairs, Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN 37232, United States
| | - Alison Richards
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - Shobana Jayapalan
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - Nikita Narayani
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - Michael P Czech
- Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States
| | - Clifford J Rosen
- Maine Health Institute for Research, Scarborough, ME 04074, United States
| | - Elizabeth Rendina-Ruedy
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
- Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, United States
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11
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Aiassa V, Ferreira MDR, Ingaramo P, D'Alessandro ME. Salvia hispanica L. (chia) seed have beneficial effects upon visceral adipose tissues extracellular matrix disorders and inflammation developed in a sucrose-rich diet-induced adiposity rodent model. Mol Cell Endocrinol 2025; 597:112438. [PMID: 39638143 DOI: 10.1016/j.mce.2024.112438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 11/29/2024] [Accepted: 12/02/2024] [Indexed: 12/07/2024]
Abstract
We have previously demonstrated that dietary Salvia hispanica L. (chia) seed, rich in α-linolenic acid (ALA), was able to reduce visceral adiposity and improves insulin sensitivity in a rodent experimental model of adiposity induced by the administration of a sucrose-rich diet (SRD). The evidence suggests that the pathological expansion of visceral adipose tissue (VAT) is accompanied by changes in the extracellular matrix (ECM) components, which can lead to fibrosis, and/or a greater expression of pro-inflammatory adipokines. The aim of the present work was to evaluate the effect of chia seed administration upon key components and modulators of ECM remodeling and inflammation in different white adipose tissues (WAT) (epididymal-eWAT- and retroperitoneal-rWAT-) in a SRD-induced adiposity rodent model. The results showed that chia seed reduced the increased hydroxyproline levels observed in SRD-fed group and this was accompanied by changes in the activity/expression of matrix metalloproteinases MMP-2 and MMP-9. No changes were observed in transforming growth factor β (TGF-β) expression levels. In addition, this nutritional intervention was able to reduce the levels of PAI-1 and MCP-1, and to increase the levels of adiponectin in both VAT. An increase in the ratio of n-3/n-6 polyunsaturated fatty acids in the membrane phospholipids of both VAT was also observed. The present study demonstrated that chia seed have anti-fibrotic and anti-inflammatory actions in the VAT which could play a key role in the amelioration of visceral adiposity and whole-body insulin insensitivity developed in SRD-fed rats.
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Affiliation(s)
- Victoria Aiassa
- Laboratorio de Estudio de Enfermedades Metabólicas Relacionadas con la Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - María Del Rosario Ferreira
- Laboratorio de Estudio de Enfermedades Metabólicas Relacionadas con la Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - Paola Ingaramo
- Instituto de Salud y Ambiente del Litoral (ISAL- CONICET), Facultad de Bioquímica y Cs. Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - María Eugenia D'Alessandro
- Laboratorio de Estudio de Enfermedades Metabólicas Relacionadas con la Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
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12
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Wali JA, Ni D, Raubenheimer D, Simpson SJ. Macronutrient interactions and models of obesity: Insights from nutritional geometry. Bioessays 2025; 47:e2400071. [PMID: 39506509 DOI: 10.1002/bies.202400071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 10/17/2024] [Accepted: 10/24/2024] [Indexed: 11/08/2024]
Abstract
The global obesity epidemic results from a complex interplay of genetic and environmental factors, with diet being a prominent modifiable element driving weight gain and adiposity. Although excess intake of energetic macronutrients is implicated in causing obesity, ongoing debate centers on whether sugar or fat or both are driving the rising obesity rates. This has led to competing models of obesity such as the "Carbohydrate Insulin Model", the "Energy Balance Model", and the "Fructose Survival Hypothesis". Conflicting evidence from studies designed to focus on individual energetic macronutrients or energy rather than macronutrient mixtures underlies this disagreement. Recent research in humans and animals employing the nutritional geometry framework (NGF) emphasizes the importance of considering interactions among dietary components. Protein interacts with carbohydrates, fats, and dietary energy density to influence both calorie intake ("protein leverage") and, directly and indirectly, metabolic physiology and adiposity. Consideration of these interactions can help to reconcile different models of obesity, and potentially cast new light on obesity interventions.
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Affiliation(s)
- Jibran A Wali
- Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia
| | - Duan Ni
- Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
- School of Medical Sciences, Chronic Diseases Theme, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - David Raubenheimer
- Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia
| | - Stephen J Simpson
- Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia
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13
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Dong J, Shelp GV, Poole EM, Cook WJJ, Michaud J, Cho CE. Prenatal choline supplementation enhances metabolic outcomes with differential impact on DNA methylation in Wistar rat offspring and dams. J Nutr Biochem 2025; 136:109806. [PMID: 39547266 DOI: 10.1016/j.jnutbio.2024.109806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 10/21/2024] [Accepted: 11/08/2024] [Indexed: 11/17/2024]
Abstract
Choline is an essential nutrient required for proper functioning of organs and serves as a methyl donor. In liver where choline metabolism primarily occurs, glucose homeostasis is regulated through insulin receptor substrates (IRS) 1 and 2. The objective of this research was to determine the role of prenatal choline as a modulator of metabolic health and DNA methylation in liver of offspring and dams. Pregnant Wistar rat dams were fed an AIN-93G diet and received drinking water either with supplemented 0.25% choline (w/w) as choline bitartrate or untreated control. All offspring were weaned to a high-fat diet for 12 weeks. Prenatal choline supplementation led to higher insulin sensitivity in female offspring at weaning as well as lower body weight and food intake and higher insulin sensitivity in female and male adult offspring compared to offspring from untreated dams. Higher hepatic betaine concentrations were observed in dams and female offspring of choline-supplemented dams at weaning and higher glycerophosphocholine in female and male offspring at postweaning compared to the untreated control, suggestive of sustaining different choline pathways. Hepatic gene expression of Irs2 was higher in dams at weaning and female offspring at weaning and postweaning, whereas Irs1 was lower in male offspring at postweaning. Gene-specific DNA methylation of Irs2 was lower in female offspring at postweaning and Irs1 methylation was higher in male offspring at postweaning that exhibited an inverse relationship between methylation and gene expression. In conclusion, prenatal choline supplementation contributes to improved parameters of insulin signaling but these effects varied across time and offspring sex.
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Affiliation(s)
- Jianzhang Dong
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Gia V Shelp
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Elizabeth M Poole
- Department of Family Relations and Applied Nutrition, University of Guelph, Guelph, Ontario, Canada
| | - William J J Cook
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Jana Michaud
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Clara E Cho
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
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14
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Almeida MM, Calviño C, Reis-Gomes CF, Lombardi I, Brand ALM, Pazos-Moura CC, Garrett R, Alves MA, Trevenzoli IH. Maternal obesity changes the small intestine endocannabinoid system and fecal metabolites of weanling rats associated with reduced intestinal permeability and impaired glucose homeostasis. J Nutr Biochem 2025; 136:109802. [PMID: 39547267 DOI: 10.1016/j.jnutbio.2024.109802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 10/18/2024] [Accepted: 11/07/2024] [Indexed: 11/17/2024]
Abstract
The small intestine, including the endocannabinoid system (ECS), regulates the energy homeostasis. If maternal obesity modifies the intestinal ECS of the offspring favoring metabolic disorders throughout life is unexplored. Regardless maternal insults, overaction of the ECS has been related to obesity, mainly via type 1 cannabinoid receptor (CB1) signaling, while type 2 cannabinoid receptor (CB2) signaling and the endocannabinoid-like compounds, such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), have been associated with anti-inflammatory effects. We hypothesized that maternal obesity changes the ECS in the small intestine of weanling rat offspring in a sex-specific manner associated with altered fecal metabolites. Female rats received a control diet (C; 9% fat) or an obesogenic diet (OD; 37.2% fat, 11.8% sucrose) 9 weeks before mating, gestation and lactation. Offspring were euthanized at weaning. Maternal obesity increased CB2 protein content and mRNA levels of monocyte chemoattractant protein-1 in the small intestine in male offspring, while decreased fecal content of PEA and OEA in both sexes. Maternal obesity decreased gut permeability, but impaired glycemic homeostasis. Concerning fecal levels of γ-aminobutyric acid, amino acids and hypoxanthine, maternal obesity induced a fecal signature related to inflammatory and glycemic homeostasis impairment and dysbiosis. Maternal obesity induced intestinal inflammation and the signaling of CB2, PEA, and OEA might be part of a counter-regulatory response, contributing to reduced gut permeability, but not enough to avoid overweight and glycemic impairment in the offspring at weaning. Our findings provide molecular insights into the intestinal and fecal biomarkers for metabolic disorders.
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Affiliation(s)
- Mariana M Almeida
- Instituto de Biofísica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil; Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Minas Gerais, Brasil.
| | - Camila Calviño
- Instituto de Biofísica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Clara F Reis-Gomes
- Instituto de Biofísica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Isabelle Lombardi
- Instituto de Biofísica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Ana Laura Macedo Brand
- Instituto de Química (IQ), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Carmen C Pazos-Moura
- Instituto de Biofísica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Rafael Garrett
- Instituto de Química (IQ), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Marina A Alves
- Instituto de Pesquisa de Produtos Naturais Walter Mors (IPPN), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Isis H Trevenzoli
- Instituto de Biofísica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
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15
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Ribeiro IT, Fioretto MN, Dos Santos SAA, Alvarez MVN, Portela LMF, Mattos R, Sebastian HB, Vitali PM, Seiva FRF, Barbisan LF, Lima CAH, Damasceno DC, Zambrano E, Justulin LA. Maternal protein restriction and postnatal sugar consumption increases inflammatory response and deregulates metabolic pathways in the liver of male offspring rats with aging. Mol Cell Endocrinol 2025; 599:112484. [PMID: 39900277 DOI: 10.1016/j.mce.2025.112484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/22/2025] [Accepted: 01/27/2025] [Indexed: 02/05/2025]
Abstract
This study investigated the late effects of maternal protein restriction (MPR) and early postnatal sugar consumption on liver health in male Sprague-Dawley rat offspring, focusing on changes observed throughout the aging process. The animals were divided into the following groups: Control (CTR): Male offspring whose dams consumed a normal protein diet (NPD, 17% protein) and water ad libitum during gestation and lactation, and then fed a NPD and water until PND 540; Control + Sugar (CTR + SUG): The same treatment as CTR, but consuming a sugar solution (10% diluted in water) from postnatal day (PND) 21-90, and then fed a NPD and water until PND 540; Gestational and Lactational Low Protein (GLLP): Male offspring whose dams consumed a low-protein diet (LPD, 6% protein) during gestation and lactation and, then fed a NPD and water ad libitum until PND 540; Gestational and Lactational Low Protein + Sugar (GLLP + SUG): male offspring whose dams consumed a LPD during gestation and lactation, and then fed a NPD and a sugar solution (10% diluted in water) ad libitum from PND 21 to 90. On PND 540, the animals were anesthetized, weighed, and euthanized, and their livers were collected for morphological and molecular analyses. The GLLP and GLLP + SUG groups showed lower body weight and lower retroperitoneal fat weight compared to the CTR and CTR + SUG groups. Morphological analysis revealed inflammatory foci in the liver from the CTR + SUG, GLLP, and GLLP + SUG groups, compared to the CTR group. Hepatic activities of CAT, SOD, and GSH-Px were increased in the GLLP + SUG group and decreased in the GLLP group, compared to the CTR group. Immunohistochemistry showed a significant increase in occupied area per foci de hepatocytes positive for GSTpi (placental form) in the CTR + SUG, GLLP, and GLLP + SUG groups, compared to the CTR group. Proteomic analysis of the groups revealed significant changes in hepatic metabolic and inflammatory pathways. In the CTR + SUG group, upregulated pathways associated with non-alcoholic fatty liver disease (NAFLD) and downregulated pathways related to autophagy were observed. In the GLLP and GLLP + SUG groups, there was a significant impact on metabolic pathways, including glucose metabolism, gluconeogenesis, glycogenesis, and cellular stress responses. An upregulation of pathways associated with chemokine- and cytokine-mediated inflammatory processes was also identified, indicating activation of the immune system in the liver during aging. Therefore, MPR, with or without postnatal sugar consumption, resulted in hepatic changes in metabolism and the antioxidant defense in old male offspring.
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Affiliation(s)
- Isabelle Tenori Ribeiro
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil.
| | - Matheus Naia Fioretto
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil
| | - Sérgio Alexandre Alcantara Dos Santos
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil; Cancer Signaling and Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
| | | | - Luiz Marcos Frediani Portela
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil
| | - Renato Mattos
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil
| | - Hecttor Baptista Sebastian
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil
| | - Pedro Menchini Vitali
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil
| | - Fábio Rodrigues Ferreira Seiva
- Department of Chemical and Biological Sciences, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil
| | - Luís Fernando Barbisan
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil
| | - Clélia Akiko Hiruma Lima
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil
| | - Débora Cristina Damasceno
- Laboratory of Experimental Research on Gynecology and Obstetrics (UNIPEX), Course of Postgraduate on Tocogynecology, Botucatu Medical School, Sao Paulo State University, Botucatu, SP, Brazil
| | - Elena Zambrano
- Department Reproductive Biology, Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City, Mexico; Facultad de Química, Universidad Nacional Autónoma de, Mexico
| | - Luis Antonio Justulin
- UNESP- Sao Paulo State University, Department of Structural and Functional Biology, Institute of Biosciences, Botucatu, SP, Brazil.
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16
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Jovanovic J, Stone ML, Dooyema SR, Tao YK, Fuhrmann S, Levine EM. Diet gel-based oral drug delivery system for controlled dosing of small molecules for microglia depletion and inducible Cre recombination in mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.23.634530. [PMID: 39896588 PMCID: PMC11785137 DOI: 10.1101/2025.01.23.634530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
Small molecules like PLX5622 for microglia depletion and Tamoxifen for inducible Cre recombination are commonly used in mouse research. Traditional application methods, such as chow or oral gavage and injections, have limitations, including uncontrolled dosage and risk of injury. To address this issue, we have developed an alternative oral drug delivery system using a gel-based rodent maintenance diet that allows for controlled consumption and adjustment of dosage and is suitable for water-insoluble small molecules. We tested DietGel® 93M (93M) infused with PLX5622 (0.8 mg/g and 2.0 mg/g) in the Cx3cr1 gfp/+ retinal microglia reporter mouse and Tamoxifen-infused 93M (0.3125 mg/g) in the Rlbp1-CreERT2 ;Rosa ai14 mouse with an inducible tdTomato reporter in retinal Müller glia. Mice were single-caged and received daily batches of PLX5622-infused 93M over 14 days or Tamoxifen-infused 93M for one or three days followed by a 14-day observation period. Longitudinal scanning laser ophthalmoscopy in vivo and fixed tissue imaging were used to track GFP and tdTomato expression. Following evaluation of a suitable 93M consumption rate (g/d) to sustain body weight, the PLX5622-93M diet at both concentrations showed a 94% microglia depletion rate at 3 days and >99% after one and two weeks. The Tamoxifen-93M diet confirmed suitability for inducible Cre recombination, with significant treatment-time dependent efficacy and a positive correlation between total Tamoxifen dose and tdTomato expression. This study demonstrates that a diet gel-based drug delivery system offers a controllable and less invasive alternative to current drug application methods for PLX5622 and Tamoxifen.
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Affiliation(s)
- Joel Jovanovic
- Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, United States
| | - Megan L Stone
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States
| | - Samantha R Dooyema
- Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, United States
| | - Yuankai K Tao
- Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, United States
- Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States
| | - Sabine Fuhrmann
- Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, United States
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States
| | - Edward M Levine
- Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, United States
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States
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17
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Patel V, Li YN, Benhamou LRE, Park HG, Raleigh M, Brenna JT, Powers JT. Ultra-High Dose Oral ω3 Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA), or Oxidation-Resistant Deuterated DHA Block Tumorigenesis in a MYCN-Driven Neuroblastoma Model. Cancers (Basel) 2025; 17:362. [PMID: 39941731 PMCID: PMC11816027 DOI: 10.3390/cancers17030362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/15/2025] [Accepted: 01/21/2025] [Indexed: 02/16/2025] Open
Abstract
Background/Objectives: Neuroblastoma is a genetically diverse, highly metastatic pediatric cancer accounting for 15% of childhood cancer deaths despite only having ~8% of childhood cancer incidence. The current standard of care for high-risk diseases is highly genotoxic. This, combined with less than 50% survival in high-risk diseases and an abysmal 5% survival in relapsed cases, makes discovering novel, effective, and less toxic treatments essential. Methods: A prophylactic syngeneic mouse model was used to test high-dose lipid-mediator highly unsaturated fatty acids on tumorigenesis. Wildtype mice were gavaged with 12.3-14.6 g/d (adult human equivalent) omega-3 EPA, DHA, or oxidation-resistant bis allylic deuterated DHA (D-DHA) and 4.6-6.0 g/d arachidonic acid (ARA). At seven days, MYCN-expressing murine neuro-2a cells syngeneic to the gavaged mice were injected subcutaneously. Oral gavage continued for 10-20 d post-injection when tumors and tissues were harvested. Results: Fifty percent of control (not gavaged) animals form tumors (4/8) at about 10 d. High-dose DHA, D-DHA, and EPA block tumor formation completely in n = 8 or 10 animals. In contrast, ω6 arachidonic acid (4.6-6.0 g/d) enhances tumor formation (6/10 tumors) and reduces latency (5.5 to 10 days) compared to the control. The co-delivery of ARA and EPA results in a reduced tumor burden analogous to the control group, suggesting that EPA directly opposes the mechanism of ARA-mediated tumor formation. DHA acts through a non-oxidative mechanism. Conclusions: Sustained high-dose ω3 (weeks/months) is safe and well-tolerated in humans. These results suggest that ω3 DHA and EPA delivery at ultra-high doses may represent a viable low-toxicity therapy for neuroblastoma.
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Affiliation(s)
- Vishwa Patel
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA; (V.P.); (M.R.)
- Dell Pediatric Research Institute, Department of Chemistry, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78723, USA; (Y.N.L.); (H.G.P.)
| | - Yan Ning Li
- Dell Pediatric Research Institute, Department of Chemistry, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78723, USA; (Y.N.L.); (H.G.P.)
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78723, USA
| | - Lorraine-Rana E. Benhamou
- Dell Pediatric Research Institute, Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX 78723, USA;
| | - Hui Gyu Park
- Dell Pediatric Research Institute, Department of Chemistry, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78723, USA; (Y.N.L.); (H.G.P.)
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78723, USA
| | - Mariya Raleigh
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA; (V.P.); (M.R.)
| | - J. Thomas Brenna
- Dell Pediatric Research Institute, Department of Chemistry, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78723, USA; (Y.N.L.); (H.G.P.)
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78723, USA
- Dell Pediatric Research Institute, Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX 78723, USA;
| | - John T. Powers
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA; (V.P.); (M.R.)
- Dell Pediatric Research Institute, Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX 78723, USA;
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Lima FDS, Santos MQD, Makiyama EN, Hoffmann C, Fock RA. The essential role of magnesium in immunity and gut health: Impacts of dietary magnesium restriction on peritoneal cells and intestinal microbiome. J Trace Elem Med Biol 2025; 88:127604. [PMID: 39884252 DOI: 10.1016/j.jtemb.2025.127604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/09/2025] [Accepted: 01/18/2025] [Indexed: 02/01/2025]
Abstract
Magnesium (Mg2+) is essential for life, and low levels impair immune function, promote chronic inflammation, and influence the intestinal microbiome, with the peritoneal cavity serving as a site for direct interaction between the cavity and intestinal contents, including the microbiota. This study investigates the effects of a Mg2+-restricted diet on peritoneal immune cells and its interplay with the intestinal microbiome. Male C57BL/6NTaq mice were divided into three groups: control, restricted, and restored. The control group received a diet containing 500 mg Mg2+/kg, the restricted group received a diet with 50 mg Mg2+/kg for four weeks, and the restored group first received the restricted diet for four weeks, followed by the control diet supplemented with 0.5 g MgCl₂ per liter of water for an additional four weeks. Results showed Mg2+ restriction did not affect body weight, food intake, or water consumption but induced hypomagnesemia, reversible upon dietary restoration. Mg2+ deficiency increased in neutrophils numbers in the blood and peritoneal cavity, indicating an inflammatory response. Gene expression analysis in peritoneal mononuclear cells revealed elevated levels of Nfkb, Stat1 and Stat3, suggesting heightened inflammatory signaling. Additionally, cytokine expression analysis showed increased levels of Tnfa, Il1b and Il10, but not Il6, in Mg2+-restricted group. The intestinal microbiome of Mg2+-restricted mice exhibited increased alpha diversity, with changes in taxa abundance, including an increase in Romboutsia ilealis and a decrease in the Oscillospiraceae and Lachnospiraceae. Mg2+ deficiency significantly affects some immune functions and gut microbiota, highlighting the importance of Mg²+ in maintaining the gut health.
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Affiliation(s)
- Fabiana da Silva Lima
- Department of Food Sciences and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Marina Quintas Dos Santos
- Department of Microbiology, Institute of Biomedical Sciences of the University of São Paulo, São Paulo, Brazil
| | - Edson Naoto Makiyama
- Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Christian Hoffmann
- Department of Food Sciences and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; Department of Microbiology, Institute of Biomedical Sciences of the University of São Paulo, São Paulo, Brazil; Food Research Center (FoRC), São Paulo, SP, Brazil.
| | - Ricardo Ambrósio Fock
- Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
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19
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Silva-Veiga FM, Marinho TS, de Souza-Mello V, Aguila MB, Mandarim-de-Lacerda CA. Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), positively impacts the altered microbiota of obese, diabetic, ovariectomized mice. Life Sci 2025; 361:123310. [PMID: 39675551 DOI: 10.1016/j.lfs.2024.123310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 11/26/2024] [Accepted: 12/11/2024] [Indexed: 12/17/2024]
Abstract
The study aimed to verify the effect of Tirzepatide (Tzp, a dual agonist GIP/GLP-1) on intestinal health and microbiota balance in an obese diabetic ovariectomized (Ovx) mice model. Female C57BL/6 mice with Ovx and diet-induced obesity with diabetes were treated with Tzp (10 nmol/kg) for four weeks. Control (C) and obese-diabetic subgroups (Od) were formed (group abbreviations: O, Ovx; T, Tzp; n = 30/group): C, CT, CO, COT, Od, OdT, OdO, OdOT. The ileum was structurally and molecularly studied, and cecal feces had microbial DNA determined. Tzp improved the intestinal barrier structure and protection. Cldn12 (Claudin 12) increased, and Muc2 (Mucin 2) decreased. JamA (junctional adhesion molecules) and Ocln (Occludin) increased. Tzp mitigated macrophage activation and inflammation, altered composition, and the contribution to microbiota: Firmicutes decreased, and Bacteroidetes increased, changing the Firmicutes / Bacteroidetes ratio. Proteobacteria, Actinobacteria, Bifidobacterium, and Clostridium increased. In addition, Bacteroides, Prevotella, and Akkermansia increased. PCA indicated a significant action of Cd14, Muc2, and Tlr4 on CO and Il17 on OdO; Il10, Cd206, Cd12, Ocln, and JamA in Od. Bacteroides, Bifidobacterium, Clostridium, Actinobacteria, and Bacteroides were enhanced in CT and COT, Provotella, Proteobacteria, and Firmicutes in CO, Od, OdT, OdO, and Akkermansia in OdOT. In conclusion, the intestinal barrier function in our model is compromised by alterations in phylogenetic diversity and intestinal microbiota, which characterize dysbiosis and potentially enable the influx of toxins into other tissues. Treatment with Tzp demonstrated the ability to reverse intestinal dysbiosis, help repair intestinal barrier integrity, and mitigate possible endotoxemia through anti-inflammatory signaling pathways.
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Affiliation(s)
- Flavia Maria Silva-Veiga
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Thatiany Souza Marinho
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Vanessa de Souza-Mello
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcia Barbosa Aguila
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Carlos Alberto Mandarim-de-Lacerda
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
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20
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Liu S, Mohri S, Tsukamoto M, Yanai Y, Manabe Y, Sugawara T. Preventive effects of dietary fucoxanthin on ultraviolet A induced photoaging in hairless mice. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2025; 105:453-464. [PMID: 39194018 DOI: 10.1002/jsfa.13842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 07/24/2024] [Accepted: 08/12/2024] [Indexed: 08/29/2024]
Abstract
BACKGROUND Repeated exposure to ultraviolet A (UVA) irradiation, which can penetrate the epidermis and reach the dermis, is one of the major causes of skin photoaging. Photoaged skin is characterized clinically by generalized wrinkling, a dry and loose appearance, and seborrheic keratoses, along with skin barrier dysfunction. Fucoxanthin, a xanthophyll carotenoid with a specific allenic bond and 5,6-monoepoxide in its structure, has been found to serve various functions as a food supplement. In the present study, the protective effects of orally administered fucoxanthin at relatively low concentrations (0.001% and 0.01%) against UVA induced photoaging were evaluated in vivo using hairless mice. RESULTS Oral supplementation of 0.001% fucoxanthin was sufficient for its metabolites to accumulate in the skin, thereby inhibiting pathological changes induced by UVA irradiation, including impaired skin barrier function and accelerated wrinkle formation. Analysis of gene expression revealed that dietary fucoxanthin exerted antiphotoaging effects, possibly by modulating natural moisturizing factor (NMF) synthesis, desquamation, and ceramide composition in the epidermis, and by inhibiting the UVA induced degradation of collagen fibers and inflammation in the dermis. CONCLUSION Taken together, our data indicate the potential application of dietary fucoxanthin as a novel ingredient in nutricosmetics for skin care against photoaging. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Shuyu Liu
- Graduate School of Agriculture, Kyoto University, Kyoto, Japan
| | - Shinsuke Mohri
- Department of Biomedical Sciences, Ritsumeikan University, Kyoto, Japan
| | | | | | - Yuki Manabe
- Graduate School of Agriculture, Kyoto University, Kyoto, Japan
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21
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Wang CY, Melgar-Bermudez E, Welch D, Dagbay KB, Bhattacharya S, Lema E, Daman T, Sierra O, Todorova R, Drame PM, Grenha R, Fisher FM, Grayson D, Lerner L, Cadena SM, Seehra J, Lachey J. A Recombinant Antibody Against ALK2 Promotes Tissue Iron Redistribution and Contributes to Anemia Resolution in a Mouse Model of Anemia of Inflammation. Am J Hematol 2025. [PMID: 39791515 DOI: 10.1002/ajh.27578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 11/06/2024] [Accepted: 12/23/2024] [Indexed: 01/12/2025]
Abstract
Patients with chronic inflammation are burdened with anemia of inflammation (AI), where inflammatory cytokines inhibit erythropoiesis, impede erythropoietin production, and limit iron availability by inducing the iron regulator hepcidin. High hepcidin hinders iron absorption and recycling, thereby worsening the impaired erythropoiesis by restricting iron availability. AI management is important as anemia impacts quality of life and potentially affects morbidity and mortality. The bone morphogenetic protein (BMP)-SMAD pathway is crucial for hepcidin regulation. Here, we characterized a research antibody against BMP receptor ALK2, RKER-216, and investigated its mechanism in suppressing hepcidin and improving anemia in acute/chronic inflammation. Additive effects of RKER-216 and recombinant human erythropoietin (rhEPO) on erythropoiesis and iron utilization were also explored. We showed that RKER-216 neutralized ALK2 activity by competing with the binding of BMP6. RKER-216 reduced hepcidin transcription in Hep3B cells, and a subcutaneous dose of RKER-216 at 3 mg/kg suppressed serum hepcidin and increased circulating iron for 3-4 days in wildtype mice. Moreover, RKER-216 decreased hepcidin by inhibiting SMAD1/5/9 signaling in lipopolysaccharide-mediated inflammation and liberated iron from the recycling pathway to alleviate anemia in mice with adenine-induced chronic kidney disease (CKD), a mouse model of AI. Finally, RKER-216 reversed iron-restricted erythropoiesis in CKD mice and supplied the iron requirement for complete resolution of anemia when coupled with rhEPO in addressing AI. Our data support that ALK2 is a key hepcidin regulator and that a neutralizing ALK2 antibody has the potential to restore iron homeostasis as monotherapy or in combination with rhEPO to ameliorate AI.
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Affiliation(s)
- Chia-Yu Wang
- Keros Therapeutics, Lexington, Massachusetts, USA
| | | | - Diana Welch
- Keros Therapeutics, Lexington, Massachusetts, USA
| | | | | | - Evan Lema
- Keros Therapeutics, Lexington, Massachusetts, USA
| | - Tyler Daman
- Keros Therapeutics, Lexington, Massachusetts, USA
| | | | | | | | - Rosa Grenha
- Keros Therapeutics, Lexington, Massachusetts, USA
| | | | - Dena Grayson
- Keros Therapeutics, Lexington, Massachusetts, USA
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22
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Rakhshandehroo M, Harvey L, de Bruin A, Timmer E, Lohr J, Tims S, Schipper L. Maternal exposure to purified versus grain-based diet during early lactation in mice affects offspring growth and reduces responsivity to Western-style diet challenge in adulthood. J Dev Orig Health Dis 2025; 16:e3. [PMID: 39780545 DOI: 10.1017/s2040174424000436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
The nutritional environment during fetal and early postnatal life has a long-term impact on growth, development, and metabolic health of the offspring, a process termed "nutritional programming." Rodent models studying programming effects of nutritional interventions use either purified or grain-based rodent diets as background diets. However, the impact of these diets on phenotypic outcomes in these models has not been comprehensively investigated. We used a previously validated (C57BL/6J) mouse model to investigate the effects of infant milk formula (IMF) interventions on nutritional programming. Specifically, we investigated the effects of maternal diet type (i.e., grain-based vs purified) during early lactation and prior to the intervention on offspring growth, metabolic phenotype, and gut microbiota profile. Maternal exposure to purified diet led to an increased post-weaning growth velocity in the offspring and reduced adult diet-induced obesity. Further, maternal exposure to purified diet reduced the offspring gut microbiota diversity and modified its composition post-weaning. These data not only reinforce the notion that maternal nutrition significantly influences the programming of offspring vulnerability to an obesogenic diet in adulthood but emphasizes the importance of careful selection of standard background diet type when designing any preclinical study with (early life) nutritional interventions.
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Affiliation(s)
| | - L Harvey
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - A de Bruin
- Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - E Timmer
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - J Lohr
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - S Tims
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - L Schipper
- Danone Research & Innovation Center, Utrecht, The Netherlands
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23
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Shahin NN, Ahmed-Farid OA, Sakr EAE, Kamel EA, Mohamed MM. Oral Supplements of Combined Lactobacillus plantarum and Asparagus officinalis Modulate Gut Microbiota and Alleviate High-Fat Diet-Induced Cognitive Deficits and Neurodegeneration in Rats. Probiotics Antimicrob Proteins 2025:10.1007/s12602-024-10429-7. [PMID: 39777720 DOI: 10.1007/s12602-024-10429-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/06/2024] [Indexed: 01/11/2025]
Abstract
High-fat diet (HFD) consumption disrupts the gut microbiome, instigating metabolic disturbance, brain pathology, and cognitive decline via the gut-brain axis. Probiotic and prebiotic supplementation have been found to improve gut microbiome health, suggesting they could be effective in managing neurodegenerative disorders. This study explored the potential benefits of the probiotic strain Lactobacillus plantarum 20174 (L. plantarum), prebiotic Asparagus officinalis (A. officinalis) extract, or their synbiotic combination against HFD-induced cognitive dysfunction and neurodegeneration in rats. Male Sprague-Dawley rats were fed either a normal diet or an HFD for 24 weeks. Starting from week 13, rats on either diet were divided into vehicle-, prebiotic-, probiotic-, and synbiotic-treated subgroups. Rats received their assigned intervention for 12 more weeks. Prebiotic, probiotic, or synbiotic treatment reverted HFD-instigated alterations in hippocampal amyloid beta, p-tau, α-synuclein, and BDNF levels, leading to restored cognitive function. The tested therapies also improved the HFD-disrupted lipid profile. Interestingly, probiotic and synbiotic therapies attenuated oxidative stress and inflammation, reinstated neurotransmitter balance, and mitigated the energy deficit in HFD-fed rats. Furthermore, L. plantarum and Asparagus administration modulated gut microbiota composition by raising Lactobacillus species and reducing Coliform and Staphylococci bacteria as well as fungi populations. These findings suggest that the oral consumption of A. officinalis prebiotics and/or L. plantarum probiotics alleviates HFD-induced cognitive deficit and neurodegeneration through modulation of the gut-brain axis with superior restorative effects being achieved by synbiotic treatment.
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Affiliation(s)
- Nancy N Shahin
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
| | | | - Ebtehag A E Sakr
- Botany Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | - Enas A Kamel
- Biochemistry and Nutrition Department, Faculty of Women for Arts Science and Education, Ain Shams University, Cairo, Egypt
| | - Maha M Mohamed
- Home Economic Department, Faculty of Women for Arts Science and Education, Ain Shams University, Cairo, Egypt
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24
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Joubert MBV, Ingaramo PI, Collins P, D'Alessandro ME. Astaxanthin improves lipotoxicity, lipid peroxidation and oxidative stress in kidney of sucrose-rich diet-fed rats. J Nutr Biochem 2025; 135:109779. [PMID: 39374743 DOI: 10.1016/j.jnutbio.2024.109779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 10/01/2024] [Accepted: 10/03/2024] [Indexed: 10/09/2024]
Abstract
Metabolic Syndrome (MS) is a cluster of metabolic risk factors, characterized by abdominal obesity, dyslipidemia, hypertension, insulin resistance, among others. The purpose of the study was to evaluate the astaxanthin (AXT) effects extracted from freshwater crab (Dilocarcinus pagei) at the Paraná Basin on lipotoxicity, lipid peroxidation and oxidative stress in the kidney of rats fed with a sucrose-rich diet (SRD). We hypothesized that daily administration of AXT prevents kidney damage by reducing lipotoxicity, lipid peroxidation, and reactive oxygen species (ROS), and by improving antioxidant enzyme defenses and crosstalk between NrF2 and NF-ĸB transcription factors. Male Wistar rats were fed a reference diet (RD), RD+AXT, SRD and SRD+AXT (AXT daily oral dose: [10 mg/kg body weight]) for 90 days. Systolic and diastolic blood pressure, biochemical assays in serum and urine were evaluated. Renal cortex samples were taken for histological analysis, determination of triglyceride content, ROS, thiobarbituric acid reactive substances (TBARS), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) enzyme activities and glutathione content (GSH). 4-HNE, NrF2, and NF-ĸB p65 expression were analyzed by immunohistochemistry. We demonstrated that daily oral supplementation of AXT to animals fed a SRD reduced systolic and diastolic blood pressure, histological renal damage, lipid accumulation, ROS and lipid peroxidation, and increased CAT and GPx activities. NrF2 protein expression in renal cortex was increased, whilst NF-ĸB p65 was reduced. AXT extracted from freshwater crabs (Dilocarcinus pagei) may be promising nutritional strategy for the prevention of renal alterations present in this model.
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Affiliation(s)
- Michelle Berenice Vega Joubert
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición, Departamento de Ciencias Biológicas, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina
| | - Paola Inés Ingaramo
- Departamento de Fisiopatología Ambiental, Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Cs. Biológicas. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina
| | - Pablo Collins
- Departamento de Acuicultura, Instituto Nacional de Limnología (INALI), Universidad Nacional del Litoral- Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET), Santa Fe, Argentina
| | - María Eugenia D'Alessandro
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición, Departamento de Ciencias Biológicas, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina.
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25
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Brishti A, Johnson SJ, Palmer DG, Raihan MO, Yan L, Casperson SL. Effects of defined voluntary running distances coupled with high-fat diet consumption on the skeletal muscle transcriptome of male mice. Physiol Rep 2025; 13:e70170. [PMID: 39821584 PMCID: PMC11738645 DOI: 10.14814/phy2.70170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 12/16/2024] [Accepted: 12/16/2024] [Indexed: 01/19/2025] Open
Abstract
Exercise counters many adverse health effects of consuming a high-fat diet (HFD). However, complex molecular changes that occur in skeletal muscle in response to exercising while consuming a HFD are not yet known. We investigated the interplay between diverse exercise regimes and HFD consumption on the adaptation of skeletal muscle transcriptome. C57BL/6 male mice were randomized into five groups-one sedentary control group and four exercise groups. The exercise groups consisted of an unrestricted running group (8.3 km/day) and three groups that were restricted to 75%, 50%, or 25% of unrestricted running (6.3, 4.2, and 2.1 km/day, respectively). Total RNA was extracted from frozen gastrocnemius muscle for transcriptome analyses. DEG counts were 1347, 1823, 1103, and 1107 and there were 107, 169, 67, and 89 unique genes present in the HFD-25%, HFD-50%, HFD-75%, and HFD-U, respectively. Comparing exercise groups, we found that exercising at 50% resulted in the most differentially expressed transcripts with the MAPK and PPAR signaling pathways enriched in down- and up-regulated genes, respectively. These results demonstrate that running distance impacts the adaptation of the skeletal muscle transcriptome to exercise and suggest that middle-distance running may provide the greatest protection against high-fat diet-induced stress coupled with exercise.
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Affiliation(s)
- Afrina Brishti
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
| | - Sarah J. Johnson
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
- Present address:
Department of Biomedical Sciences, School of Medicine and Health SciencesUniversity of North DakotaGrand ForksNorth DakotaUSA
| | - Daniel G. Palmer
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
| | - Md Obayed Raihan
- Department of Pharmaceutical Sciences, College of Health Sciences and PharmacyChicago State UniversityChicagoIllinoisUSA
| | - Lin Yan
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
| | - Shanon L. Casperson
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
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26
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Iwai K, Norikura T. Simultaneous ingestion of apple pectin enhances the absorption and antioxidant activity of quercetin in rats. Food Sci Biotechnol 2025; 34:277-285. [PMID: 39758731 PMCID: PMC11695566 DOI: 10.1007/s10068-024-01657-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 05/12/2024] [Accepted: 07/01/2024] [Indexed: 01/07/2025] Open
Abstract
The enhanced bioavailability of quercetin (Qr), which has low absorption, may have beneficial effects on human health. This study aimed to elucidate the effects of simultaneous pectin ingestion on the absorption and antioxidant activity of Qr. Qr concentrations in the plasma and urine of rats fed Qr + cellulose or Qr + pectin diets were determined, and thiobarbituric acid reactive substances (TBARS) in oxidized low-density lipoprotein (LDL) were measured. The concentrations of Qr and its metabolites in the plasma and urine increased one day after feeding the Qr + pectin diet compared with the Qr + cellulose diet. The elevation of TBARS was suppressed in rats fed the Qr + pectin diet. Qr concentrations in the plasma and LDL increased in a dose-dependent manner with pectin. Qr levels in plasma and LDL were negatively correlated with TBARS levels in LDL. The simultaneous ingestion of pectin has been suggested to immediately enhance the absorption and antioxidant activity of Qr.
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Affiliation(s)
- Kunihisa Iwai
- Department of Applied Biology and Food Sciences, Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki, Aomori 036-8561 Japan
| | - Toshio Norikura
- Department of Nutrition, Faculty of Health Sciences, Aomori University of Health and Welfare, 58-1 Mase, Hamadate, Aomori 030-8505 Japan
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Grases-Pintó B, Torres-Castro P, Abril-Gil M, Castell M, Rodríguez-Lagunas MJ, Pérez-Cano FJ, Franch À. TGF-β2, EGF and FGF21 influence the suckling rat intestinal maturation. J Nutr Biochem 2025; 135:109778. [PMID: 39374742 DOI: 10.1016/j.jnutbio.2024.109778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 09/04/2024] [Accepted: 10/01/2024] [Indexed: 10/09/2024]
Abstract
Some of the growth factors present in breast milk, such as transforming growth factor-β (TGF-β), epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), play important roles in the development of the intestinal tract. The aim of this study was to determine the effect of a supplementation with TGF-β2, EGF and FGF21 on suckling rats intestinal maturation. For this purpose, Wistar rats were supplemented daily with TGF-β2, EGF or FGF21 throughout the suckling period. We evaluated the functionality of the intestinal epithelial barrier through an in vivo dextran permeability assay, and by a histomorphometric and immunohistochemical study. In addition, the intestinal gene expression of tight junction-associated proteins, mucins, toll-like receptors, and maturation markers was analyzed. Moreover, the intraepithelial lymphocyte (IEL) phenotypical composition was established. During the suckling period, the supplementation with TGF-β2, EGF and FGF21 showed important signs of intestinal maturation. These results suggest that these molecules, present in breast milk, play a modulatory role in the maturation of the intestinal barrier function and the IEL composition during the suckling period.
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Affiliation(s)
- Blanca Grases-Pintó
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain
| | - Paulina Torres-Castro
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain
| | - Mar Abril-Gil
- Klinikum rechts der Isar, Institute of Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University of Munich, Munich, Germany
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain
| | - María J Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain
| | - Francisco J Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain.
| | - Àngels Franch
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA·UB), Santa Coloma de Gramenet, Spain
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Illesca PG, Ferreira MDR, Benmelej A, D'Alessandro ME. Salvia hispanica L. (chia) seed improves redox state and reverts extracellular matrix collagen deposition in skeletal muscle of sucrose-rich diet-fed rats. Biofactors 2025; 51:e2087. [PMID: 38804965 DOI: 10.1002/biof.2087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 05/13/2024] [Indexed: 05/29/2024]
Abstract
Skeletal muscle (SkM) is a plastic and dynamic tissue, essential in energy metabolism. Growing evidence suggests a close relationship between intramuscular fat accumulation, oxidative stress (OS), extracellular matrix (ECM) remodeling, and metabolic deregulation in SkM. Nowadays natural products emerge as promising alternatives for the treatment of metabolic disorders. We have previously shown that chia seed administration reverts SkM lipotoxicity and whole-body insulin resistant (IR) in sucrose-rich diet (SRD) fed rats. The purpose of the present study was to assess the involvement of OS and fibrosis in SkM metabolic impairment of insulin-resistant rats fed a long-term SRD and the effects of chia seed upon these mechanisms as therapeutic strategy. Results showed that insulin-resistant SRD-fed rats exhibited sarcopenia, increase in lipid peroxidation, altered redox state, and ECM remodeling-increased collagen deposition and lower activity of the metalloproteinase 2 (MMP-2) in SkM. Chia seed increased ferric ion reducing antioxidant power and glutathione reduced form levels, and the activities of glutathione peroxidase and glutathione reductase enzymes. Moreover, chia seed reversed fibrosis and restored the MMP-2 activity. This work reveals a participation of the OS and ECM remodeling in the metabolic alterations of SkM in our experimental model. Moreover, current data show novel properties of chia seed with the potential to attenuate SkM OS and fibrosis, hallmark of insulin-resistant muscle.
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Affiliation(s)
- Paola G Illesca
- Laboratorio de Estudio de Enfermedades Metabólicas Relacionadas con la Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - María Del R Ferreira
- Laboratorio de Estudio de Enfermedades Metabólicas Relacionadas con la Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - Adriana Benmelej
- Cátedra de Morfología Normal, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina
| | - María Eugenia D'Alessandro
- Laboratorio de Estudio de Enfermedades Metabólicas Relacionadas con la Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
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29
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Peixoto TC, Quitete FT, Teixeira AVS, Martins BC, Soares RDA, Atella GC, Bertasso IM, Lisboa PC, Resende AC, Mucci DDB, Souza-Mello V, Martins FF, Daleprane JB. Palm and interesterified palm oil-enhanced brown fat whitening contributes to metabolic dysfunction in C57BL/6J mice. Nutr Res 2025; 133:94-107. [PMID: 39705913 DOI: 10.1016/j.nutres.2024.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 11/22/2024] [Accepted: 11/22/2024] [Indexed: 12/23/2024]
Abstract
Palm oil is widely used in the food industry owing to its high stability and versatility. The interesterified version has been used as an alternative to oils rich in trans fatty acids. However, the health effects of these vegetable oils are not yet fully understood. We hypothesized that the consumption of palm oil (noninteresterified and interesterified), even without excessive amounts of energy and lipids in the diet, could lead to morphofunctional changes in brown adipose tissue (BAT). To this end, male C57BL/6J mice were divided into 3 dietary groups (n = 10 each): soybean oil (SO), palm oil (PO), and interesterified palm oil (IPO) for 10 weeks. The PO and IPO groups had significant increases in the visceral fat mass and interscapular BAT (iBAT) lipid content. In iBAT, the PO and IPO groups showed lower mRNA expression of Ucp1, Adrb3, and Pgc1a, while the PO also showed lower mRNA levels of Ppara and Ampk, and the IPO showed lower Prdm16 expression. Moreover, PO had higher Il6 expression and lower catalase activity, while the IPO showed an upregulated Tnfa expression and lower catalase activity, but higher antioxidant activity of the glutathione peroxidase (GPx) enzyme. The consumption of PO and IPO had negative effects on weight and body fat, including the impairment of iBAT function. Our findings give rise to apprehensions regarding the safety and consequences of consuming PO and IPO for energy metabolism.
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MESH Headings
- Animals
- Palm Oil/pharmacology
- Mice, Inbred C57BL
- Adipose Tissue, Brown/metabolism
- Adipose Tissue, Brown/drug effects
- Male
- Soybean Oil/administration & dosage
- Soybean Oil/pharmacology
- Mice
- Plant Oils/pharmacology
- Intra-Abdominal Fat/metabolism
- Uncoupling Protein 1/metabolism
- RNA, Messenger/metabolism
- Transcription Factors/metabolism
- Transcription Factors/genetics
- Adipose Tissue, White/metabolism
- Adipose Tissue, White/drug effects
- Interleukin-6/metabolism
- Receptors, Adrenergic, beta-3/metabolism
- Receptors, Adrenergic, beta-3/genetics
- Diet
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
- Lipid Metabolism/drug effects
- Catalase/metabolism
- DNA-Binding Proteins
- PPAR alpha
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Affiliation(s)
- Thamara Cherem Peixoto
- Laboratory for Interaction Studies between Nutrition and Genetics, Department of Basic and Experimental Nutrition, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Fernanda Torres Quitete
- Laboratory of Cardiovascular Pharmacology and Medicinal Plants, Department of Pharmacology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Ananda Vitoria Silva Teixeira
- Laboratory for Interaction Studies between Nutrition and Genetics, Department of Basic and Experimental Nutrition, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Bruna Cadete Martins
- Laboratory for Interaction Studies between Nutrition and Genetics, Department of Basic and Experimental Nutrition, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Ricardo de Andrade Soares
- Laboratory of Cardiovascular Pharmacology and Medicinal Plants, Department of Pharmacology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Geórgia Correa Atella
- Medical Biochemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Iala Milene Bertasso
- Laboratory of Endocrine Physiology, Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Patrícia Cristina Lisboa
- Laboratory of Endocrine Physiology, Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Angela Castro Resende
- Laboratory of Cardiovascular Pharmacology and Medicinal Plants, Department of Pharmacology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Daniela de Barros Mucci
- Laboratory for Interaction Studies between Nutrition and Genetics, Department of Basic and Experimental Nutrition, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Vanessa Souza-Mello
- Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Fabiane Ferreira Martins
- Laboratory for Interaction Studies between Nutrition and Genetics, Department of Basic and Experimental Nutrition, Rio de Janeiro State University, Rio de Janeiro, Brazil; Department of Morphology, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil
| | - Julio Beltrame Daleprane
- Laboratory for Interaction Studies between Nutrition and Genetics, Department of Basic and Experimental Nutrition, Rio de Janeiro State University, Rio de Janeiro, Brazil.
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Men D, Dai J, Lei Z, Tian L, Wang Z, Sheng J, Tian Y, Tao L. Preparation, characterization, stability and replenishing calcium ability of Moringa oleifera leaf peptide-calcium chelates. Food Res Int 2025; 200:115439. [PMID: 39779097 DOI: 10.1016/j.foodres.2024.115439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 10/26/2024] [Accepted: 11/26/2024] [Indexed: 01/11/2025]
Abstract
Calcium deficiency has garnered significant attention as a global public health issue. A new generation of calcium supplements, peptide-calcium chelates, is expected to increase in market value. In this study, we produced MORP (MW < 1 kDa) from Moringa oleifera leaf protein via enzymatic hydrolysis for chelation with Ca2+ to produce MORP-Ca. SEM, EDS, FTIR and FS characterized the structure of MORP-Ca. The results indicate alterations in both the appearance and internal structure of MORP following calcium chelation. The functional groups of N-H, C-H, C-N, -C = O, -COO-, C-O, and -OH in MORP are involved in chelating Ca2+ to form MORP-Ca. In addition, MORP-Ca exhibits poor stability in the stomach; however, it demonstrates high stability in the intestine and under various temperature conditions. The results of the cellular experiments demonstrated that MORP-Ca is an effective promoter of calcium transport and absorption. MORP-Ca effectively increased bone mineral density and improved bone formation in animal studies. In addition, MORP-Ca supplementation improved the gut microbiota imbalance in rats fed a calcium-deficient diet, resulting in an increase in Firmicutes and a decrease in Actinobacteria. Thus, there is a connection between altered gastrointestinal flora and calcium absorption. LC-MS/MS and molecular docking analyses identified ARNEGRDL, RELIIGDR, YTPDYETK, YYTPDYETK, and IKFEFPAVDTL as key peptide sequences for the calcium-supplementing role of MORP (MW < 1 kDa). These results establish a theoretical foundation for the use of MORP-Ca as a calcium supplement or functional food.
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Affiliation(s)
- Deying Men
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China
| | - Jiahe Dai
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China; National Research and Development Professional Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming 650201, China; Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; Yunnan Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650201, China
| | - Zhongyuan Lei
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China
| | - Lingyan Tian
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China
| | - Zilin Wang
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China
| | - Jun Sheng
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China; National Research and Development Professional Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming 650201, China
| | - Yang Tian
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China; National Research and Development Professional Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming 650201, China; Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; Yunnan Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650201, China; Puer University, Puer 665000, China.
| | - Liang Tao
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China; National Research and Development Professional Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming 650201, China; Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; Yunnan Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650201, China.
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Lee MS, Doo M, Kim IH, Kim Y. Effects of Capsicum Oleoresin on the Energy Expenditure and Mitochondrial Content of Brown Adipose Tissue in Mice Fed a High-Fat Diet. Prev Nutr Food Sci 2024; 29:422-429. [PMID: 39759824 PMCID: PMC11699576 DOI: 10.3746/pnf.2024.29.4.422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/09/2024] [Accepted: 10/28/2024] [Indexed: 01/07/2025] Open
Abstract
Capsicum oleoresin (CO) is a concentrated extract derived from peppers (Capsicum annum L.) containing capsaicin (the active compound responsible for its pungency) and other bioactive components. The present study aimed to determine whether CO affects the energy expenditure and mitochondrial content of brown adipose tissue (BAT) in diet-induced obese mice. Four-week-old C57BL/6J mice were divided into three groups and fed with a normal chow diet, 45% high-fat diet (HF), or HF supplemented with 0.01% CO (HF+CO) for 16 weeks. The results showed that CO supplementation significantly suppressed weight gain and improved serum lipid profiles compared with HF feeding. The energy expenditure was significantly higher in the HF+CO group than in the HF group. Compared with the HF group, the HF+CO group had significantly upregulated the messenger RNA expression levels of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in BAT. The mitochondrial DNA content, which was reduced by HF intake, was significantly restored in the HF+CO group. Furthermore, the mitochondrial size and number were restored in the HF+CO group than in in the HF group. The activity of adenosine monophosphate-activated protein kinase (AMPK) in BAT was significantly increased in the HF+CO group than in the HF group. In conclusion, CO potentially inhibits weight gain by increasing energy expenditure in diet-induced obese mice. This beneficial effect is likely associated with the enhancement of mitochondrial content by upregulating key markers, including UCP1, PGC-1α, and AMPK, in BAT.
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Affiliation(s)
- Mak-Soon Lee
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea
| | - Miae Doo
- Department of Food and Nutrition, Kunsan National University, Gunsan 54150, Korea
| | - In-Hwan Kim
- Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul 02841, Korea
| | - Yangha Kim
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea
- Graduate Program in System Health Science and Engineering, Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea
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32
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da Fonseca STO, Alves CC, Dias CT, Mendes-da-Silva C. Probiotics and undernourishment impact on brain 5-Hydroxytryptamine system and neurotrophin BDNF in rats: Risk of depression and anxiety? Nutrition 2024; 132:112680. [PMID: 39904121 DOI: 10.1016/j.nut.2024.112680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 11/14/2024] [Accepted: 12/26/2024] [Indexed: 02/06/2025]
Abstract
BACKGROUND Undernourishment can significantly affect the serotonergic system, potentially increasing the risk of neuropsychiatric disorders such as depression and anxiety. Probiotic therapy has emerged as a potential modulator of the serotonergic system and brain-derived neurotrophic factor (BDNF). Our hypothesis posits that probiotic treatment positively influences the serotonergic system and BDNF levels in the prefrontal cortex (PFC) and hippocampus (HIP), mitigating the effects of malnutrition. METHODS We conducted an experiment using 38 adult isogenic rats, divided into four groups: nourished control (n = 9), undernourished control (n = 9), nourished probiotic (n = 10), and undernourished probiotic (n = 10). The animals experienced undernourishment for 10 days, followed by probiotic supplementation while continuing food restriction for an additional 15 days. On the 25th day of the experiment, we euthanized the animals, microdissected their brains, and extracted samples from the HIP and PFC. We performed immunoblotting analysis to assess the expression levels of the following proteins: BDNF, tryptophan hydroxylase 2 enzyme, and 5-HT1A and 5-HT2C serotonergic receptors. RESULTS Our findings revealed the following effects of probiotic administration: tryptophan hydroxylase 2 expression increased in the PFC of nourished rats (P = 0.033) and in the HIP of undernourished rats (P = 0.013); improved 5-HT2C expression was observed in the PFC under both nutritional conditions (P < 0.01). The proBDNF levels were elevated in the HIP of undernourished rats (P = 0.001). CONCLUSION Probiotic administration effectively modulated the gut-microbiota-brain axis by enhancing serotonergic system proteins in the prefrontal cortex and hippocampus of both nourished and undernourished rats.
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Affiliation(s)
| | - Cláudia Cristina Alves
- Department of Biosciences, Clinical and Experimental Nutrition Research Laboratory, Federal University of São Paulo, Santos, São Paulo, Brazil
| | - Clarissa Tavares Dias
- Department of Biosciences, Laboratory of Neuroscience and Nutrition, Federal University of São Paulo, Santos, São Paulo, Brazil
| | - Cristiano Mendes-da-Silva
- Department of Biosciences, Laboratory of Neuroscience and Nutrition, Federal University of São Paulo, Santos, São Paulo, Brazil.
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33
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Zhu T, Kuai Y, Guo X, Bu G, Yang C, Chen F. Effect of Dietary Oils with Different Fatty Acid Compositions on Serum Lipid and Gut Microbiota of Rats. Foods 2024; 14:61. [PMID: 39796351 PMCID: PMC11720656 DOI: 10.3390/foods14010061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 12/22/2024] [Accepted: 12/27/2024] [Indexed: 01/13/2025] Open
Abstract
The effects of three dietary oils (rapeseed oil, camellia oil, linseed oil) with different fatty acid compositions on the growth performance, digestion and gut microbiota of SD rats after 8 weeks of feeding were studied. The serum metabolic index and liver histomorphology of rats were measured using an automatic biochemical analyzer and light microscope. Furthermore, 16S rDNA amplicon sequencing technology was used to analyze the gut microbiota. It was found that these differences in fatty acid composition had no significant effect on body fat and liver tissue. However, after digestion, the rapeseed oil group showed lowest triglyceride content (1.22 ± 0.15) and a lower LDL/HDL ratio (0.41 ± 0.02). For gut microbiota distribution, the linseed oil group showed a higher Firmicutes/Bacteroides ratio (6.11 ± 0.54) and a high proportion of Lactobacillus. These data indicate that both the unsaturated fatty acid content and n-3 unsaturated fatty acids collectively had an effect on digestion metabolism, and the influence order may be n-3 unsaturated fatty acids > unsaturated fatty acid content.
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Affiliation(s)
| | | | | | | | | | - Fusheng Chen
- College of Food Science and Engineering, Henan University of Technology, Zhengzhou 450001, China; (T.Z.); (Y.K.); (X.G.); (G.B.); (C.Y.)
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34
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Essa HA, Hashim AF, Abdel-Aziz NN, Mohamed FEZS, Ali AM. Olive and Linseed Oil Blend-Based Nanoemulsions Fortified With Ginger Extract Nutraceutical: Mitigating Liver Fibrosis Induced by Carbon Tetrachloride by Regulating Oxidative Stress and TGF-β/MMP9 Signaling Pathway in Rats. Mol Nutr Food Res 2024:e202400497. [PMID: 39723735 DOI: 10.1002/mnfr.202400497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 11/02/2024] [Accepted: 11/27/2024] [Indexed: 12/28/2024]
Abstract
Liver fibrosis is a significant contributor to global morbidity and mortality, making the identification of non-toxic natural therapies to slow its progression essential. This study evaluated the anti-fibrotic potential of a nutraceutical blend comprising extra virgin olive oil, linseed oil, and ginger extract, formulated in both emulsion and nanoemulsion forms, using a rat model of liver fibrosis. Nanoemulsions were prepared using the ultrasonication technique, and their particle size and stability were analyzed via the DLS method. Twenty-four male albino rats were divided into four groups: normal control, CCl4-treated, oil emulsion-treated, and nanoemulsion-treated. Liver fibrosis was induced by oral administration of carbon tetrachloride (CCl4), while the emulsions were administered daily alongside CCl4 for four weeks. Liver function indices, oxidative stress biomarkers, and gene expressions were assessed, along with histopathological and immunohistochemical analyses. The results revealed that both emulsions significantly improved liver function, enhanced antioxidant capacity, and reduced lipid peroxidation. They downregulated pro-fibrogenic markers (TGF-β1, TIMP-1) and upregulated anti-fibrogenic markers (MMP9, HGF), leading to a reduction in liver fibrosis. The nanoemulsion exhibited superior efficacy compared to the emulsion. These findings demonstrate that the nutraceutical blend, particularly in nanoemulsion form, effectively attenuated liver fibrosis and improved hepatic health markers. This underscores its potential as a natural therapy for liver fibrosis and related conditions, emphasizing its nutritional value in supporting liver health.
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Affiliation(s)
- Hend A Essa
- Nutrition and Food Sciences Department, Food Industries and Nutrition Research Institute, National Research Centre, Dokki, Cairo, Egypt
| | - Ayat F Hashim
- Fats and Oils Department, Food Industries and Nutrition Research Institute, National Research Centre, Dokki, Cairo, Egypt
| | - Nahla N Abdel-Aziz
- Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Dokki, Cairo, Egypt
| | - Fatma El-Zahraa Sayed Mohamed
- Nutrition and Food Sciences Department, Food Industries and Nutrition Research Institute, National Research Centre, Dokki, Cairo, Egypt
| | - Alaa M Ali
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
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Fan J, Wang X, Wang Y, Song J, Chen M, Weng C, Wang L, Chi Z, Zhang W. Dietary glutamine supplementation improves both Th1 and Th17 responses via CARD11-mTORC1 pathway in murine model of atopic dermatitis. Int Immunopharmacol 2024; 143:113316. [PMID: 39368135 DOI: 10.1016/j.intimp.2024.113316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 09/29/2024] [Accepted: 10/01/2024] [Indexed: 10/07/2024]
Abstract
Glutamine (GLN) is considered an immunomodulatory nutrient, while caspase recruitment domain 11 (CARD11) is a susceptibility locus for atopic dermatitis (AD). T-cell antigen receptor (TCR)-stimulated GLN uptake requires CARD11. However, the specific pathogenesis of AD via GLN uptake remains unclear. This study aimed to elucidate the association between dietary GLN supplementation and the CARD11 pathway in the pathogenesis of AD, focusing on T helper type 1 (Th1) and Th17 cell expression in AD. Herein, wild-type (WT) mice with house dust mite epidermal-sensitized skin exhibited increased expression of interferon-gamma (IFN-gamma) and interleukin (IL)-17, whereas CARD11 deficiency impaired Th1 and Th17 responses at the same site. CARD11 is a key mediator of Th1 and Th17 expression in AD. Additionally, we suppressed mammalian target of rapamycin complex 1 (mTORC1) signaling, downstream of CARD11, to underscore the critical role of CARD11 in mediating Th1 and Th17 expression in AD. Further, dietary supplementation of GLN to CARD11-/- mice restored Th1 and Th17 responses, whereas inflammatory expression was reduced in WT mice, and p-CARD11 expression and mTORC1 signaling activity were increased in JPM50.6 cells and CARD11-/- mice. Upon inhibiting the GLN transporter, alanine-serine-cysteine transporter carrier 2 (ASCT2), we observed that the Th1 and Th17 response in AD was reduced. Conclusively, ASCT2-mediated GLN uptake improves the expression of Th1 and Th17 cells via CARD11-mTORC1 signaling pathway in AD, suggesting the potential of glutamine supplementation for AD treatment.
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Affiliation(s)
- Junwen Fan
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Xiaoming Wang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Yufei Wang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Jingjing Song
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Mingxin Chen
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Cuiye Weng
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Lei Wang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Zailong Chi
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou 325027, China.
| | - Weixi Zhang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
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Elmoslemany AM, Rehan M, Safhi FA, Zeima NM, El-Hassnin MF, Elnaggar SA, Almami IS, Zedan A. The Antioxidant and Anti-Inflammatory Impacts of Purple and White Eggplants on Fertility and Expression of Fertility-Related Genes in Rats Treated With Aluminum Chloride. J Toxicol 2024; 2024:8215321. [PMID: 39734607 PMCID: PMC11681986 DOI: 10.1155/jt/8215321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 11/19/2024] [Accepted: 11/28/2024] [Indexed: 12/31/2024] Open
Abstract
The environmental xenobiotic aluminum chloride (AlCl3) destroys reproduction via free radicals. The present study aimed at evaluating the impact of purple and white eggplant on rat fertility when exposed to AlCl3. A total of 36 male albino rats were divided into six groups: a negative control, the second given AlCl3 (17 mg/kg b.w.) for 28 days, the third and fourth given a basal diet with 5% and 10% white eggplant powder, and the fifth and sixth given a basal diet with 5% and 10% purple eggplant powder. AlCl3 reduced follicular-stimulating hormone (FSH), plasma testosterone, sperm count, motility, and viability, luteinizing hormone (LH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities. On the contrary, malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) disclosed considerable increases. Besides, reproductive hormones, antioxidant enzymes, and sperm quality were significantly enhanced in the treated groups with eggplants. A downregulation in the expression of Fkbp6, Ccna1, and Cyp19A1 was detected, and normal expression was restored after treatment with high dose from eggplant (10%) without significant differences, whereas Msh4 and Cdk2 genes continued in their down expression and measured decrease up to 60% in Msh4 and 40% in Cdk2 in their mRNA levels after treatment with high dosage from eggplant, respectively. Alternatively, rats treated with eggplant at high dose (10%) gained more body weight (33%) and much bigger testicles (1.30 ± 0.05 g) when compared to AlCl3-treated rats (gained only 16% more body weight and 1.04 ± 0.06 g testis weight) after 28 days, subsequently, the eggplant reduced the side effect of AlCl3-induced toxicity. AlCl3 induced broad cytotoxic effects in seminiferous tubules, and the antioxidant and anti-inflammatory activities of eggplant minimized the histological alteration in rat testes.
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Affiliation(s)
- Amira M. Elmoslemany
- Department of Nutrition & Food Science, Faculty of Home Economy, Al-Azhar University, Tanta 31512, Egypt
| | - Medhat Rehan
- Department of Plant Production, College of Agriculture and Food, Qassim University, Burydah 51452, Saudi Arabia
| | - Fatmah Ahmed Safhi
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Neveen M. Zeima
- Department of Nutrition & Food Science, Faculty of Home Economy, Al-Azhar University, Tanta 31512, Egypt
| | - Marwa Fawzy El-Hassnin
- Department of Nutrition & Food Science, Faculty of Home Economy, Al-Azhar University, Tanta 31512, Egypt
| | - Sabry Ali Elnaggar
- Department of Zoology, Faculty of Science, Tanta University, Tanta 31512, Egypt
| | - Ibtesam S. Almami
- Department of Biology, College of Science, Qassim University, Buraydah 52571, Saudi Arabia
| | - Amina Zedan
- Department of Agriculture Botany (Genetics), Faculty of Agriculture (Girls Branch), Al-Azhar University, Cairo, Egypt
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Nossar LF, Lopes JA, Pereira-Acácio A, Costa-Sarmento G, Rachid R, Wendt CHC, Miranda K, Galina A, Rodrigues-Ferreira C, Muzi-Filho H, Vieyra A. Chronic undernutrition impairs renal mitochondrial respiration accompanied by intense ultrastructural damage in juvenile rats. Biochem Biophys Res Commun 2024; 739:150583. [PMID: 39182354 DOI: 10.1016/j.bbrc.2024.150583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/08/2024] [Accepted: 08/20/2024] [Indexed: 08/27/2024]
Abstract
This study investigated whether chronic undernutrition alters the mitochondrial structure and function in renal proximal tubule cells, thus impairing fluid transport and homeostasis. We previously showed that chronic undernutrition downregulates the renal proximal tubules (Na++K+)ATPase, the main molecular machine responsible for fluid transport and ATP consumption. Male rats received a multifactorial deficient diet, the so-called Regional Basic Diet (RBD), mimicking those used in impoverished regions worldwide, from weaning to a juvenile age (3 months). The diet has a low content (8 %) of poor-quality proteins, low lipids, and no vitamins compared to control (CTR). We investigated citrate synthase activity, mitochondrial respiration (oxygraphy) in phosphorylating and non-phosphorylating conditions with different substrates/inhibitors, potential across the internal membrane (Δψ), and anion superoxide/H2O2 formation. The data were correlated with ultrastructural alterations evaluated using transmission electron microscopy (TEM) and focused ion beam scanning electron microscopy (FIB-SEM). Citrate synthase activity decreased (∼50 %) in RBD rats, accompanied by a similar reduction in respiration in non-phosphorylating conditions, maximum respiratory capacity, and ATP synthesis. The Δψ generation and its dissipation after carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone remained unmodified in the survival mitochondria. H2O2 production increased (∼100 %) after Complex II energization. TEM demonstrated intense matrix vacuolization and disruption of cristae junctions in a subpopulation of RBD mitochondria, which was also demonstrated in the 3D analysis of FIB-SEM tomography. In conclusion, chronic undernutrition impairs mitochondrial functions in renal proximal tubules, with profound alterations in the matrix and internal membrane ultrastructure that culminate with the compromise of ATP supply for transport processes.
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Affiliation(s)
- Luiz F Nossar
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Jarlene A Lopes
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Amaury Pereira-Acácio
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; Graduate Program of Translational Biomedicine, University of Grande Rio, Duque de Caxias, 25071-202, Brazil
| | - Glória Costa-Sarmento
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Rachel Rachid
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Camila H C Wendt
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Institute of Science and Technology for Structural Biology and Bioimaging/INBEB, Rio de Janeiro, 21941-902, Brazil
| | - Kildare Miranda
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Institute of Science and Technology for Structural Biology and Bioimaging/INBEB, Rio de Janeiro, 21941-902, Brazil
| | - Antonio Galina
- Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Clara Rodrigues-Ferreira
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Humberto Muzi-Filho
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Adalberto Vieyra
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; Graduate Program of Translational Biomedicine, University of Grande Rio, Duque de Caxias, 25071-202, Brazil; National Institute of Science and Technology for Regenerative Medicine/REGENERA, Rio de Janeiro, 21941-902, Brazil.
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Wang C, Zhu H, Zhang M, Zhu L, Zheng W, Lu W, Niu Y, Zhang Y, Gao B, Yu LL. Ninety-Day Subchronic Toxicology of Individual and Combined Toxicants from the Thermal Processing of Lipid-Rich Foods. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:28122-28137. [PMID: 39638751 DOI: 10.1021/acs.jafc.4c07892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
Oxidative derivatives of triacylglycerols (ox-TGs), aldehydes, and 3-monochloropropane-1,2-diol esters (3-MCPDE) were simultaneously evaluated in a 90-day subchronic study, focusing on biological indicators, biochemical indicators, and serum metabolomics as the first part of integrated toxicity and interactions. After 90 days of feeding Kunming mice, coexposure to combined toxicants significantly inhibited the trend of liver weight gain, reduced the levels of total bilirubin (TBIL) and direct bilirubin (DBIL), and decreased uric acid (UA) compared to individual toxicant exposure. A total of 21 and 31 biomarkers in female and male mice were identified, respectively. Co-exposure to combined toxicants might mitigate the changes in cytidine, CDP, dUMP, and dUDP involved in purine and pyrimidine metabolism caused by a single exposure, but exacerbate the changes in l-tryptophan, 5-hydroxy-l-tryptophan, and 5-hydroxyindoleacetic acid, which are involved in tryptophan metabolism. These results provided new insights into a comprehensive toxicity and interaction evaluation model of multiple combined toxicants in food.
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Affiliation(s)
- Chenxu Wang
- Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hanshu Zhu
- Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Miao Zhang
- Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Lin Zhu
- Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Wenhao Zheng
- Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Weiying Lu
- Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Yuge Niu
- Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Yaqiong Zhang
- Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Boyan Gao
- Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Liangli Lucy Yu
- Department of Nutrition and Food Science, University of Maryland, College Park, Maryland 20742, United States
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Iyer J, Marsh TS, Fisher RJ, Verma V. Nutrient Stability in NASA Spaceflight Experiment Rodent Food Bars. Foods 2024; 13:4093. [PMID: 39767035 PMCID: PMC11675554 DOI: 10.3390/foods13244093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 11/21/2024] [Accepted: 11/28/2024] [Indexed: 01/11/2025] Open
Abstract
The Nutrient-upgraded Rodent Food Bar (NuRFB) is the standard diet for mice in NASA's Rodent Research Project aboard the International Space Station (ISS). Given the nature of spaceflight and the lengthy production process of the food bars, a shelf-life assessment was conducted to evaluate nutritional stability over time (ranging from 0 to 27 months) and under different storage conditions (refrigerated, ambient, and refrigerated + ambient), where ambient is 22-23 °C. Lipid oxidation markers and fat- and water-soluble vitamins were assessed under various time and temperature conditions using AOAC International methods. Vitamin D levels showed a minor decrease, and riboflavin fluctuated slightly over time, but all vitamin levels remained above National Research Council (NRC) minimum requirements. Food bars stored at 4 °C showed significantly higher thiamine levels than the bars that underwent some degree of ambient temperature storage, but all met the NRC guidelines. Minimal lipid oxidation was observed for up to 18 months, and no mold or yeast growth occurred despite the high moisture content of the bars. This study confirms that NuRFBs maintain stable vitamin and lipid oxidation indices, ensuring adequate nutrition for rodents during spaceflight.
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Affiliation(s)
- Janani Iyer
- Universities Space Research Association, Mountain View, CA 94043, USA
- KBR, Houston, TX 77002, USA
- Space Biosciences, NASA Ames Research Center, Moffett Field, CA 94035, USA
| | - Tyler S Marsh
- KBR, Houston, TX 77002, USA
- Space Biosciences, NASA Ames Research Center, Moffett Field, CA 94035, USA
| | - Ryan J Fisher
- Space Biosciences, NASA Ames Research Center, Moffett Field, CA 94035, USA
| | - Vandana Verma
- Space Biosciences, NASA Ames Research Center, Moffett Field, CA 94035, USA
- ASRC Federal Space and Defense, 7000 Muirkirk Meadows Drive, Beltsville, MD 20705, USA
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de Ramos FC, Barth R, Santos MR, Almeida MDS, Ferreira SM, Rafacho A, Boschero AC, dos Santos GJ. Hepatocyte nuclear factor 4-α is necessary for high fat diet-induced pancreatic β-cell mass expansion and metabolic compensations. Front Endocrinol (Lausanne) 2024; 15:1511813. [PMID: 39741884 PMCID: PMC11685084 DOI: 10.3389/fendo.2024.1511813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 12/04/2024] [Indexed: 01/03/2025] Open
Abstract
Aims This study investigates the role of Hepatocyte Nuclear Factor 4α (HNF4α) in the adaptation of pancreatic β-cells to an HFD-induced obesogenic environment, focusing on β cell mass expansion and metabolic adaptations. Main methods We utilized an HNF4α knockout (KO) mouse model, with CRE-recombinase enzyme activation confirmed through tamoxifen administration. KO and Control (CTL) mice were fed an HFD for 20 weeks. We monitored body weight, food intake, glucose tolerance, insulin sensitivity, and insulinemia. Also, to assess structural and metabolic changes, histological analyses of pancreatic islets and liver tissue were conducted. Key findings KO mice displayed lower fasting blood glucose levels compared to CTL mice after tamoxifen administration, indicating impaired glucose-regulated insulin secretion. HFD-fed KO mice consumed less food but exhibited greater weight gain and perigonadal fat accumulation, reflecting higher energy efficiency. Histological analysis revealed more pronounced liver steatosis and fibrosis in KO mice on HFD. Glucose intolerance and insulin resistance were exacerbated in KO mice, highlighting their inability to adapt to increased metabolic demand. Structural analysis showed that KO mice failed to exhibit HFD-induced β cell mass expansion, resulting in reduced islet diameter and number, confirming the critical role of HNF4α in β cell adaptation. Significance This study demonstrates that HNF4α is essential for the proper metabolic and structural adaptation of pancreatic β-cells in response to an obesogenic environment. The lack of HNF4α impairs β cell functionality, leading to increased susceptibility to glucose intolerance and insulin resistance. These findings underscore the importance of HNF4α in maintaining glucose homeostasis and highlight its potential as a therapeutic target for diabetes management in obesity.
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Affiliation(s)
- Francieli Caroline de Ramos
- Islet Biology and Metabolism Lab – IBM Lab, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil
| | - Robson Barth
- Islet Biology and Metabolism Lab – IBM Lab, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil
| | - Marcos Rizzon Santos
- Islet Biology and Metabolism Lab – IBM Lab, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil
| | - Milena dos Santos Almeida
- Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil
| | - Sandra Mara Ferreira
- Laboratory of Endocrine Pancreas And Metabolism - LAPEM, Department of Structural and Functional Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, Brazil
| | - Alex Rafacho
- Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil
| | - Antônio Carlos Boschero
- Laboratory of Endocrine Pancreas And Metabolism - LAPEM, Department of Structural and Functional Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, Brazil
| | - Gustavo Jorge dos Santos
- Islet Biology and Metabolism Lab – IBM Lab, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil
- Laboratory of Endocrine Pancreas And Metabolism - LAPEM, Department of Structural and Functional Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, Brazil
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Morais VND, Moreira LDPD, Gomes MJC, Grancieri M, Lucio HG, Toledo RCL, Mishima MDV, Costa NMB, da Silva BP, Stampini Duarte Martino H. Chia Oil ( Salvia hispanica L.) Improves the Intestinal Health of Wistar Rats Fed a Hypercaloric Diet. JOURNAL OF THE AMERICAN NUTRITION ASSOCIATION 2024:1-10. [PMID: 39689242 DOI: 10.1080/27697061.2024.2431271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 10/04/2024] [Accepted: 11/13/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND A diet rich in fat and sugar is present in society everyday life, leading to the development of metabolic changes, especially in intestinal microbiota. Chia oil is a source of alpha-linolenic acid, which has antioxidant and anti-glycemic effects. Based on this, we hypothesized that chia oil may promote intestinal health. OBJECTIVE The study aims to investigate the effects of chia oil on gut microbiota and intestinal health in Wistar rats fed a high-fat and high-fructose diet (HFHF). METHODS The animals were separated into two groups and received the following diets: standard murine diet (AIN-93M) (n = 10) and HFHF (n = 20) to induce metabolic changes (phase I) during eight weeks. After that, the AIN-93M group remained unchanged, while the HFHF group was divided into two groups: HFHF (n = 10) and HFHF with chia oil (HFHF+CO) (n = 10) for ten weeks (phase II, chia oil treatment). We analyzed immunoglobulin A (IgA) levels, cecal pH, short-chain fatty acids (SCFAs), intestinal permeability, intestinal microbiome composition, histomorphometry, and murinometric parameters. RESULTS Chia oil consumption increased alpha-linolenic acid intake, IgA levels, propionic acid production, cecum weight, goblet cell number, thickness and depth of intestinal crypts, and the thickness of both circular and longitudinal muscle layers of the colon, and decreased cecal pH. No change was observed in the alpha and beta diversity between the HFHF and HFHF+CO groups. The HFHF+CO diet increased the relative abundance of genera Lactobacillus sp., Faecalibacterium sp., and Erysipelatoclostridium sp., compared to the AIN-93M group. No difference was observed in the intestinal permeability among the groups. CONCLUSION Chia oil consumption is an alternative for improving the intestinal health of rats fed a HFHF diet.
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Affiliation(s)
- Violeta Nunes de Morais
- Department of Nutrition and Health, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil
| | | | | | - Mariana Grancieri
- Department of Pharmacy and Nutrition, Center for Exact, Natural and Health Sciences, Federal University of Espírito Santo, Alegre, Espírito Santo, Brazil
| | - Haira Guedes Lucio
- Department of Nutrition and Health, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil
| | | | | | - Neuza Maria Brunoro Costa
- Department of Pharmacy and Nutrition, Center for Exact, Natural and Health Sciences, Federal University of Espírito Santo, Alegre, Espírito Santo, Brazil
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Origüela V, Gázquez A, López-Andreo MJ, Bueno-Vargas P, Vurma M, López-Pedrosa JM, Leyshon BJ, Kuchan M, Chan JP, Larqué E. Effects of new lipid ingredients during pregnancy and lactation on rat offspring brain gene expression. Food Funct 2024. [PMID: 39660590 DOI: 10.1039/d4fo04425h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2024]
Abstract
Maternal dietary fat intake during pregnancy and lactation may influence the bioavailability of essential lipophilic nutrients, such as docosahexaenoic acid (DHA), that are important for both the mother and her child's development. This study aimed to evaluate the effects of different maternal fat diets on fat absorption and pup brain development by analyzing gene expression. Rats were fed diets with different lipid matrices during pregnancy and lactation: diet A, mono and diglycerides (MDG) + soy lecithin phospholipids (PL); diet B, MDG + soy lecithin PL + milk-derived PL; and a control diet. All diets contained the same amount of DHA. We determined maternal dietary fat absorption, as well as the offspring fatty acid (FA) profile in both plasma and brain samples at birth and in pups at 14 days post-natal. In addition, microarray analysis was performed to characterize the pup brain gene expression. Maternal dietary fat and DHA apparent absorption was enhanced only with diet B. However, we observed higher plasma DHA and total FA concentrations in lactating pups from the experimental groups A and B compared to the control. Both brain DHA and total FA concentrations were also higher in fetuses and 14-day-old pups from group A with respect to the control, with diet B following the same trend. Offspring brain gene expression was affected by both diets A and B, with changes observed in synaptic and developmental processes in the fetuses, and the detoxification process in 14-day-old pups. Incorporating MDG and PL-rich lipid matrices into maternal diets during pregnancy and lactation may be highly beneficial for ensuring proper neurodevelopment of the fetus and newborn.
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Affiliation(s)
- Valentina Origüela
- Department of Physiology, Faculty of Biology, University of Murcia, Campus of Espinardo, 30100 Murcia, Spain.
- Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain
| | - Antonio Gázquez
- Department of Physiology, Faculty of Biology, University of Murcia, Campus of Espinardo, 30100 Murcia, Spain.
- Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain
| | - María José López-Andreo
- Molecular Biology Section, Scientific and Technical Research Area (ACTI), University of Murcia, 30100 Murcia, Spain
| | - Pilar Bueno-Vargas
- Research and Development Department, Abbott Nutrition, 18004 Granada, Spain
| | - Mustafa Vurma
- Research and Development Department, Abbott Nutrition, Columbus, 43215 Ohio, USA
| | | | - Brian J Leyshon
- Research and Development Department, Abbott Nutrition, Columbus, 43215 Ohio, USA
| | - Matthew Kuchan
- Research and Development Department, Abbott Nutrition, Columbus, 43215 Ohio, USA
| | - Jia Pei Chan
- Research and Development Department, Abbott Nutrition, Columbus, 43215 Ohio, USA
| | - Elvira Larqué
- Department of Physiology, Faculty of Biology, University of Murcia, Campus of Espinardo, 30100 Murcia, Spain.
- Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain
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Mordant A, Blakeley-Ruiz JA, Kleiner M. Stable isotope fingerprinting can directly link intestinal microorganisms with their carbon source and captures diet-induced substrate switching in vivo. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.12.10.627769. [PMID: 39713332 PMCID: PMC11661160 DOI: 10.1101/2024.12.10.627769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
Diet has strong impacts on the composition and function of the gut microbiota with implications for host health. Therefore, it is critical to identify the dietary components that support growth of specific microorganisms in vivo. We used protein-based stable isotope fingerprinting (Protein-SIF) to link microbial species in gut microbiota to their carbon sources by measuring each microbe's natural 13C content (δ13C) and matching it to the 13C content of available substrates. We fed gnotobiotic mice, inoculated with a 13 member microbiota, diets in which the 13C content of all components was known. We varied the source of protein, fiber or fat to observe 13C signature changes in microbial consumers of these substrates. We observed significant changes in the δ13C values and abundances of specific microbiota species, as well as host proteins, in response to changes in 13C signature or type of protein, fiber, and fat sources. Using this approach we were able to show that upon switching dietary source of protein, fiber, or fat (1) some microbial species continued to obtain their carbon from the same dietary component (e.g., protein); (2) some species switched their main substrate type (e.g., from protein to carbohydrates); and (3) some species might derive their carbon through foraging on host compounds. Our results demonstrate that Protein-SIF can be used to identify the dietary-derived substrates assimilated into proteins by microbes in the intestinal tract; this approach holds promise for the analysis of microbiome substrate usage in humans without the need of substrate labeling. Significance The gut microbiota plays a critical role in the health of animals including humans, influencing metabolism, the immune system, and even behavior. Diet is one of the most significant factors in determining the function and composition of the gut microbiota, but our understanding of how specific dietary components directly impact individual microbes remains limited. We present the application of an approach that measures the carbon isotope "fingerprint" of proteins in biological samples. This fingerprint is similar to the fingerprint of the substrate used to make the proteins. We describe how we used this approach in mice to determine which dietary components specific intestinal microbes use as carbon sources to make their proteins. This approach can directly identify components of an animal's diet that are consumed by gut microbes.
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Affiliation(s)
- Angie Mordant
- Department of Plant and Microbial Biology, North Carolina State University, Raleigh NC
| | | | - Manuel Kleiner
- Department of Plant and Microbial Biology, North Carolina State University, Raleigh NC
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Mohamed DA, Mabrok HB, Ramadan AA, Elbakry HF. The potential role of alkaline diets in prevention of calcium oxalate kidney stone formation. Food Funct 2024; 15:12033-12046. [PMID: 39563640 DOI: 10.1039/d4fo03567d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2024]
Abstract
Formation of kidney stones is considered a major global problem. Diet plays an important role in the management of kidney stone formation. The main goal of the present research was to evaluate the protective role of fruit and vegetable mixtures as models of an alkaline diet on formation of kidney stones in rats and to conduct molecular docking study. The chemical compositions, phenolic compound profile, β-carotene content, vitamin C and antioxidant activity of both mixtures were assessed. Fruit (-42.419 ) and vegetable (-11.13) mixtures recorded a negative potential renal acid load in the presence of macro-/micro-nutrients, β-carotene and phenolic compounds; chlorogenic acid was the major content in both mixtures. Both mixtures exhibited high antioxidant activity. Molecular docking study proved that rutin displayed the highest binding affinities for glycolate oxidase (-11.8 kcal mol-1) and lactate dehydrogenase (-10.1 kcal mol-1). The kidney stone model in rats exhibited metabolic acidosis in the urinary profile through reduction of citrate; Ca, Mg and K excretion and elevation of oxalate, creatinine, creatinine clearance, uric acid, urea and protein. Additionally, there was a significant reduction in plasma Ca, Mg and K levels, while liver and kidney function parameters improved significantly. Fruit and vegetable mixtures as models of an alkaline diet proved improvement in all the parameters. Histopathological examination of kidney sections of the kidney stone model showed crystal deposition, inflammation, and severe necrosis. Kidney sections of alkaline diet models indicated mild and moderate changes. Conclusion: The results of this study proved that both alkaline diet models were effective in protecting against kidney stone formation in vivo and in molecular docking studies.
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Affiliation(s)
- Doha A Mohamed
- Nutrition and Food Sciences Department, Food Industries and Nutrition Institute, National Research Centre, Dokki 12622, Cairo, Egypt.
| | - Hoda B Mabrok
- Nutrition and Food Sciences Department, Food Industries and Nutrition Institute, National Research Centre, Dokki 12622, Cairo, Egypt.
| | - Asmaa A Ramadan
- Nutrition and Food Sciences Department, Food Industries and Nutrition Institute, National Research Centre, Dokki 12622, Cairo, Egypt.
| | - Hagar F Elbakry
- Nutrition and Food Sciences Department, Food Industries and Nutrition Institute, National Research Centre, Dokki 12622, Cairo, Egypt.
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Li Y, Han C, Shi L, Chen C, Zhao J, Liu T, Zhuo Q. Ninety-Day Feeding Test of Stacked DBN9936 × DBN9501 Maize on Sprague Dawley Rats. J Appl Toxicol 2024. [PMID: 39639739 DOI: 10.1002/jat.4733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 10/29/2024] [Accepted: 11/12/2024] [Indexed: 12/07/2024]
Abstract
The transgenic maize DBN9936 × DBN9501, which confers resistance to insects and tolerance to herbicides, was developed via conventional cross breeding of transgenic maize DBN9936 and DBN9501. In our present study, a 90-day feeding toxicity study was conducted on Sprague Dawley rats to evaluate the safety of the maize. A total of 140 rats were randomly assigned to seven groups (n = 10/sex/group): one control group, three genetically modified (GM) groups with 17.5%, 35%, and 70% (wt/wt) GM maize, respectively, and three non-GM groups with corresponding incorporation rate of parental maize DBN318. The rats of control group were fed with AIN93G diet. The parameters including body weights, food consumption, hematology, serum biochemistry, organ weights, and histopathology were examined during the course of the study. Compared with the non-GM group or AIN93G control group, minor statistical differences were observed for some parameters in some groups, yet none of them was considered a GM-related adverse effect. In conclusion, the results demonstrated that no adverse effect was observed on rats following 90 days feeding with diet containing up to 70% GM maize. The results indicated that stacked maize DBN9936 × DBN9501 was as safe as its parental DBN318 maize.
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Affiliation(s)
- Yan Li
- Key Laboratory of Trace Element Nutrition of National Health Commission (NHC), National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Chao Han
- Key Laboratory of Trace Element Nutrition of National Health Commission (NHC), National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lili Shi
- Key Laboratory of Trace Element Nutrition of National Health Commission (NHC), National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Chen Chen
- Key Laboratory of Trace Element Nutrition of National Health Commission (NHC), National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jinpeng Zhao
- Key Laboratory of Trace Element Nutrition of National Health Commission (NHC), National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Tingting Liu
- Key Laboratory of Trace Element Nutrition of National Health Commission (NHC), National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Qin Zhuo
- Key Laboratory of Trace Element Nutrition of National Health Commission (NHC), National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China
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Nagagata BA, Mandarim-de-Lacerda CA, Aguila MB. Melatonin-Supplemented Obese Female Mice Show Less Inflammation in Ovarian Adipocytes and Browning in Subcutaneous Adipocytes. Cell Biochem Funct 2024; 42:e70034. [PMID: 39707618 DOI: 10.1002/cbf.70034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/24/2024] [Accepted: 12/10/2024] [Indexed: 12/23/2024]
Abstract
We hypothesized that melatonin (Mel) supplementation may offer therapeutic benefits for obesity, particularly in women. Therefore, the study evaluated Mel's effects on white adipose tissue (WAT) in diet-induced obese female mice. Four-week-old C57BL/6 females were assigned to either a control diet (C group) or a high-fat diet (HF group) for 6 weeks (n = 20/group). Following this, Mel was administered (10 mg/kg/day) for 8 weeks (n = 10/group), resulting in four groups: C, CMel, HF, and HFMel. The HF group developed obesity. HFMel displayed reduced fat pad size, lower plasma insulin, and improved glucose tolerance and insulin resistance compared to HF. In ovarian WAT (oWAT), HFMel versus HF showed reduced pro-inflammatory markers, less endoplasmic reticulum (ER) stress, and smaller adipocyte size. In subcutaneous WAT (sWAT), HFMel versus HF demonstrated increased adipocyte multiloculation, higher uncoupling protein-1 expression, and elevated thermogenic gene expression. Principal component analysis of gene expressions in oWAT and sWAT revealed significant differences: in oWAT, ER stress and inflammation markers were linked to the HF group, while HFMel and CMel clustered together, indicating a beneficial Mel effect. In sWAT, HFMel and CMel clustered on the opposite side of HF, which is associated with thermogenic gene expressions. In conclusion, the findings demonstrate that Mel supplementation in obese female mice, even when maintained on an HF diet, effectively modulated weight gain and reduced ovarian and subcutaneous fat accumulation. Mel supplementation positively influenced insulin resistance, inflammation, and ER stress while promoting thermogenesis in WAT in obese female mice.
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Affiliation(s)
- Brenda A Nagagata
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carlos A Mandarim-de-Lacerda
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcia Barbosa Aguila
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
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de Souza EA, Mennitti LV, Santamarina AB, Minari TP, Jucá A, Sertorio MN, Pisani LP. Maternal preconception glucose intolerance and fatty acid intake from conception to weaning: impact on offspring energy homeostasis in both male and female. Eur J Nutr 2024; 63:3013-3024. [PMID: 39231868 DOI: 10.1007/s00394-024-03485-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 08/25/2024] [Indexed: 09/06/2024]
Abstract
Environmental factors in the early life stages can lead the descendant to adaptations in gene expression, permanently impacting several structures and organs. The amount and quality of fatty acids in the maternal diet in pregnancy and lactation were found to impact offspring metabolism. So, maternal diet and insulin resistance can affect the male and female descendants through distinct pathways and at different time points. We hypothesized that maternal high-fat diet (HFD) intake before conception and an adequate amount of different fatty acids intake during pregnancy and lactation could influence the energy homeostasis system of 21-day-old offspring. Female rats received control diet (C) or HFD (HF) for 8 weeks before pregnancy. During pregnancy and lactation C group remained with same diet (C-C), HF group were distributed into 4 groups and received C diet (HF-C), normolipidic diet based on saturated fatty acids (HF-S) or based on polyunsaturated fatty acids n-3 (HF-P) or remained in same diet (HF-HF). Maternal HFD in preconception, pregnancy, and lactation (HF-HF) led to lower glucagon-like peptide-1 levels in male (HF-HF21) compared to other groups (C-C21, HF-C21, and HF-P21) and compared to HF-HF21 females. Neuropeptide YY levels were higher in the HF-HF21, HF-C21, and HF-S21 male offspring compared to HF-P21. HF-P21 was similar to C-C21. Positive correlations were found among the energy homeostasis markers genes expressed in the offspring hypothalamus. Maternal diet changes to adequate quantities of fatty acids during pregnancy and lactation showed less impaired results but was not entirely avoided. A maternal diet based on PUFA n-3 during pregnancy and lactation seems to reverse the damage of an HFD in preconception. These results of homeostasis energy system disturbance in the offspring at weaning give us clues about changes that precede the onset of the disease in adult life - adding notes to the knowledge for future investigations of prevention and treatment of chronic diseases.
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Affiliation(s)
- Esther Alves de Souza
- Biosciences Department, Institute of Health and Society, Federal University of São Paulo, Campus Baixada Santista - UNIFESP, Santos, São Paulo, Brazil
| | - Laís Vales Mennitti
- Biosciences Department, Institute of Health and Society, Federal University of São Paulo, Campus Baixada Santista - UNIFESP, Santos, São Paulo, Brazil
- Institute of Metabolic Science, Metabolic Research Laboratories, Department of Clinical Biochemistry, University of Cambridge, Cambridge, CB2 OQQ, UK
| | - Aline Boveto Santamarina
- Biosciences Department, Institute of Health and Society, Federal University of São Paulo, Campus Baixada Santista - UNIFESP, Santos, São Paulo, Brazil
| | - Tatiana Palotta Minari
- Department of Diabetes, Hypertension, and Obesity, State Faculty of Medicine in São José do Rio Preto (FAMERP), Medical School, São José do Rio Preto, São Paulo, Brazil
| | - Andrea Jucá
- Biosciences Department, Institute of Health and Society, Federal University of São Paulo, Campus Baixada Santista - UNIFESP, Santos, São Paulo, Brazil
| | - Marcela Nascimento Sertorio
- Biosciences Department, Institute of Health and Society, Federal University of São Paulo, Campus Baixada Santista - UNIFESP, Santos, São Paulo, Brazil
| | - Luciana Pellegrini Pisani
- Biosciences Department, Institute of Health and Society, Federal University of São Paulo, Campus Baixada Santista - UNIFESP, Santos, São Paulo, Brazil.
- 136, Nutrition and Endocrine Physiology Laboratory, Biosciences Department, 311, 3th floor, Vila Mathias, Santos, 11015021, SP, Brazil.
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48
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Reis-Barbosa PH, Mandarim-de-Lacerda CA. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) plus glucagon-like peptide type 1 receptor combination is more effective than SGLT2i plus dipeptidyl peptidase-4 inhibitor combination in treating obese mice metabolic dysfunction-associated steatotic liver disease (MASLD). Fundam Clin Pharmacol 2024; 38:1059-1068. [PMID: 38923017 DOI: 10.1111/fcp.13024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 06/11/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Monotherapy to treat obesity-associated liver insult is limited. OBJECTIVES In diet-induced obese mice showing metabolic dysfunction-associated steatotic liver disease (MASLD), we aimed to compare the combinations of sodium-glucose cotransporter-2 inhibitor (SGLT2i, empagliflozin, E), dipeptidyl peptidase-4 inhibitor (DPP4i, linagliptin, L), and glucagon-like peptide type 1 receptor agonist (GLP1RA, dulaglutide, D). METHODS Male 3-month-old C57BL/6J mice were fed for 12 weeks in a control (C, n = 10) or high-fat (HF, n = 30) diet. Then, mice were followed for three additional weeks: C, HF, HF E + L, and HF E + D (n = 10/group). RESULTS HF versus C showed higher hepatic triacylglycerol (TAG, +82%), steatosis (+850%), glucose intolerance (+71%), insulin (+98%), and insulin resistance (+68%). Compared to the HF group, HF E + L showed lower glucose intolerance (-60%), insulin (-61%), insulin resistance (-46%), TAG (-61%), and steatosis (-58%), and HF E + D showed lower glucose intolerance (-71%), insulin (-58%), insulin resistance (-62%), TAG (-61%), and steatosis (-82%). The principal component analysis (PCA) placed the HF group and the HF E + D group on opposite sides, while the HF E + L group was placed between C and HF E + D. CONCLUSION PCA separated the groups considering the metabolism-related genes (glucose and lipid), mitochondrial biogenesis, and steatosis. The two pharmacological combinations showed beneficial effects in treating obesity and MASLD. However, the combination of SGLT2i and GLP1RA showed more potent beneficial effects on MASLD than SGLT2i and DPP4i and, therefore, should be the recommended combination.
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Affiliation(s)
- Pedro H Reis-Barbosa
- Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carlos A Mandarim-de-Lacerda
- Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
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Aljumayi H, Alrasheedi AA, Aljutaily T, Mohamed Ahmed IA, Khalil NA. Mushroom and Kefir Functional Characterizations: Hypolipidemia and Gut Microbiota Modulations in Rat Models. Food Sci Nutr 2024; 12:10181-10193. [PMID: 39723083 PMCID: PMC11666911 DOI: 10.1002/fsn3.4503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 07/17/2024] [Accepted: 09/14/2024] [Indexed: 12/28/2024] Open
Abstract
Hyperlipidemia is a malnutrition disease associated with different lifestyle factors mainly high fat/cholesterol foods consumption and less physical activity. Consumption of high fiber foods (prebiotic sources) additionally to gut microbiota (GM; probiotics species) could overcome hyperlipidemia and its associated risks. Prebiotics and probiotics are known by protective effects in different diseases like diabetes, inflammatory bowel diseases, and cardiovascular diseases. Mushroom and kefir milk (KM) are known for their high pre/probiotic nutritional values depending on many factors, for example, eating levels and/or conditions. Therefore, this study aimed to measure the potential health benefits of dried powdered mushrooms (DPM) supplemented with KM between hyperlipidemia rats in association with lipid profile, atherogenic index (AI), and GM profile. Rats were randomly divided into main negative control healthy group (G1; -ve), positive control hyperlipidemia (G2; +ve) and three hyperlipidemia groups (G3:G5) fed DPM at 2.5%, 5%, and 10% of rats' diet additionally to 5% KM (DPM + 5% KM) each, respectively. The collected blood samples used for glucose, lipid profile (cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), and AI in addition to fecal sample for GM and short-chain fatty acids (SCFAs). Collected data illustrated that body weight, blood glucose, lipid profile, GM (Bifidobacteria and Lactobacillus vs. Clostridium histolyticum), AI, and SCFAs were improved between hyperlipidemia fed 5% both PDM + KM (p ≤ 0.05) at the best levels. In conclusion, same DPM/KM levels have broad development as functional active foods that could lower hyperlipidemia incidence and promotes intestinal health; however, much more human studies are needed.
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Affiliation(s)
- Huda Aljumayi
- Department of Food Science and Nutrition, College of SciencesTaif UniversityTaifSaudi Arabia
| | - Amani A. Alrasheedi
- Department of Food and Nutrition, Faculty of Human Sciences and DesignKing Abdulaziz UniversityJeddahSaudi Arabia
| | - Thamer Aljutaily
- Department of Food Science and Human Nutrition, College of Agriculture and FoodQassim UniversityBuraydahSaudi Arabia
| | - Isam A. Mohamed Ahmed
- Department of Food Science and Nutrition, College of Food and Agricultural SciencesKing Saud UniversityRiyadhSaudi Arabia
- Department of Food Science and Technology, Faculty of AgricultureUniversity of KhartoumShambatSudan
| | - Nazeha A. Khalil
- Nutrition and Food Sciences Department, Faculty of Home EconomicsMenoufia UniversityShibin el KomEgypt
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50
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Heine LK, Rajasinghe LD, Wagner JG, Lewandowski RP, Li QZ, Richardson AL, Tindle AN, Shareef JJ, Harkema JR, Pestka JJ. Subchronic intranasal lipopolysaccharide exposure induces pulmonary autoimmunity and glomerulonephritis in NZBWF1 mice. Autoimmunity 2024; 57:2370536. [PMID: 38976509 PMCID: PMC11289745 DOI: 10.1080/08916934.2024.2370536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 06/16/2024] [Indexed: 07/10/2024]
Abstract
Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 μg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.
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Affiliation(s)
- Lauren K. Heine
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
| | - Lichchavi D. Rajasinghe
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
| | - James G. Wagner
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States
| | - Ryan P. Lewandowski
- Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States
| | - Quan-Zhen Li
- Department of Immunology and Internal Medicine, IIMT Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Alexa L. Richardson
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
| | - Ashleigh N. Tindle
- Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States
| | - Jenan J. Shareef
- Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States
| | - Jack R. Harkema
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States
| | - James J. Pestka
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
- Department of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, MI, United States
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