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Valera RJ, Hossain MS, Patnaik R, Valdivieso C, Montorfano L, Parlade A, Augustin T, Walsh RM, Simpfendorfer CH, Roy M. Retrospective analysis of surgical pancreatic necrosectomy outcomes in patients with and without obesity. Surgery 2025; 184:109410. [PMID: 40373503 DOI: 10.1016/j.surg.2025.109410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 04/02/2025] [Accepted: 04/16/2025] [Indexed: 05/17/2025]
Abstract
BACKGROUND Acute necrotizing pancreatitis is associated with high morbidity and mortality. This study aims to compare surgical necrosectomy outcomes in acute necrotizing pancreatitis between patients with and without obesity. METHODS A retrospective chart review was performed for all patients who underwent surgical necrosectomy via a minimally invasive approach or an open approach over a 10-year period at a large US healthcare system. Patients were divided into 2 groups: those with obesity (body mass index ≥30 kg/m2) and those without obesity (body mass index <30 kg/m2). The primary end point was the incidence of early complications or postoperative death within 30 and 90 days. The secondary end point was the incidence of long-term complications. RESULTS In total, 80 patients were included with 36 (45%) with obesity, and 44 (55%) without obesity. A total of 52 patients (65%) had an open approach and 28 (35%) had an minimally invasive approach. The average age was 54.79 ± 15.25 years, and the median follow-up time was 83.5 days (interquartile range, 40.25-149.75 days). The median body mass index of the patient group with obesity was 34.55 kg/m2 (interquartile range, 31.55-40.61), and that for the patient group without obesity was 25.97 kg/m2 (interquartile range, 23.22-28.35 kg/m2) (P ≤ .0001). Days from admission to surgical intervention was longer in obese patients but it was not statistically significant (44.50 [interquartile range, 12-88] vs 27 [interquartile range, 15-42.5], P = .831). 30 and 90-day complication rates and mortality were similar between the groups. CONCLUSION Operative outcomes of pancreatic necrosectomy in patients with obesity appears to be comparable with patients without obesity. Surgical pancreatic necrosectomy can be performed safely, effectively, and in a similar time frame regardless of the presence of obesity.
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Affiliation(s)
- Roberto J Valera
- Department of General Surgery, Section of Hepatobiliary and Pancreatic Surgery, Cleveland Clinic Florida, Weston, FL. https://twitter.com/Valera
| | - Mir Shanaz Hossain
- Department of General Surgery, Section of Hepatobiliary and Pancreatic Surgery, Cleveland Clinic, Cleveland, OH
| | - Ronit Patnaik
- Department of General Surgery, University of Texas Health Science Center, San Antonio, TX
| | - Cesar Valdivieso
- Department of General Surgery, Section of Hepatobiliary and Pancreatic Surgery, Cleveland Clinic Florida, Weston, FL
| | - Lisandro Montorfano
- Department of General Surgery, Section of Hepatobiliary and Pancreatic Surgery, Cleveland Clinic Florida, Weston, FL. https://twitter.com/Montorfano
| | - Albert Parlade
- Department of Imaging, Cleveland Clinic Florida, Weston, FL
| | - Toms Augustin
- Department of General Surgery, Section of Hepatobiliary and Pancreatic Surgery, Cleveland Clinic, Cleveland, OH. https://twitter.com/Augustin
| | - R Matthew Walsh
- Department of General Surgery, Section of Hepatobiliary and Pancreatic Surgery, Cleveland Clinic, Cleveland, OH
| | - Conrad H Simpfendorfer
- Department of General Surgery, Section of Hepatobiliary and Pancreatic Surgery, Cleveland Clinic Florida, Weston, FL
| | - Mayank Roy
- Department of General Surgery, Section of Hepatobiliary and Pancreatic Surgery, Cleveland Clinic Florida, Weston, FL.
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Vieira A, Abatti M, Michels M, Goulart A, Faller CJ, Borges H, Fernandes F, Dominguini D, Rocha L, Córneo E, Dias R, Dal-Pizzol F. The Impact of Biological Sex And High-Fat High-Fructose Diet on Brain Dysfunction in an Animal Model of Sepsis. Mol Neurobiol 2025:10.1007/s12035-025-04937-y. [PMID: 40268828 DOI: 10.1007/s12035-025-04937-y] [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: 01/02/2024] [Accepted: 04/08/2025] [Indexed: 04/25/2025]
Abstract
The aim of this study was to evaluate long-term inflammatory, biochemical and behavioral parameters in adult male and female Wistar rats submitted to a model of high-fat and high fructose diet and sepsis. In the study we used 8-month-old male and female rats. High-fat and high fructose diet was provided for 4 months, and sepsis was induced shortly afterwards. Behavioral tests were performed at 10, 30 and 60 days after sepsis induction, at 30- and 60-days metabolic parameters, leptin and cytokines (prefrontal cortex and hippocampus) were determined. High-fat and high-fructose diet was able to induce glucose intolerance. Sepsis favored anxious behavior at 10 days after sepsis, remaining at 30 days and with apparent improvement at 60 days in females and maintenance of behavior in males. Cognitive damage was observed both at 30 and 60 days in animals from both groups. Plasma metabolic parameters were elevated only males exposed to a high-fat high-fructose diet and submitted to CLP only at 30 days. Long-term brain inflammation was not consistently affected both by sex and high-fat and high fructose diet.The relationship between high-fat and high fructose diet, gender and sepsis is still contradictory, as are the mechanisms involved in this paradox. Models and analyses need to be standardized in order to better understand how this event occurs.
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Affiliation(s)
- Andriele Vieira
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
- UNESC - Universidade do Extremo Sul Catarinense, PPGCS - Programa de Pós-graduação em Ciências da Saúde, Endres: Av. Universitária, Bairro Universitário, Criciúma, SC, 1105, Brazil.
| | - Mariane Abatti
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Monique Michels
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Amanda Goulart
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Cristiano Julio Faller
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Heloisa Borges
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Filipe Fernandes
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Diogo Dominguini
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Luana Rocha
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Emily Córneo
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Rodrigo Dias
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Felipe Dal-Pizzol
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
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Bhuia MS, Chowdhury R, Hasan R, Hasan MSA, Ansari SA, Ansari IA, Mubarak MS, Coutinho HDM, Domiciano CB, Islam MT. trans-Ferulic Acid Antagonizes the Anti-Inflammatory Activity of Etoricoxib: Possible Interaction of COX-1 and NOS. Biotechnol Appl Biochem 2025. [PMID: 39985155 DOI: 10.1002/bab.2739] [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: 05/13/2024] [Accepted: 02/06/2025] [Indexed: 02/24/2025]
Abstract
This study emphasizes to investigate the modulatory activity of trans-ferulic acid (TFA) on anti-inflammatory activity of etoricoxib (ETO) and underlying mechanisms via formalin-induced licking and paw edema model and in silico study. Inflammation was induced by injecting formalin (50 µL) into the right hind paw of mice. The animals were treated with different doses of TFA (25, 50, and 75 mg/kg, p.o.). The vehicle and ETO (35 mg/kg, p.o.) were provided as positive and negative control, respectively. ETO also served combined with TFA to evaluate the modulatory activity. The licking behavior was counted for the early and late phases, whereas the paw edema diameter was measured by using a slide caliper. All treatment was continued for 7 days until the edema was totally minimized to determine the inflammation's recovery capability for a specific group. Different computed and web tools were used to estimate molecular binding affinity, binding interactions, and pharmacokinetics. The findings demonstrated that TFA significantly (p < 0.05) enhanced the onset of licking and reduced the number of licks compared to vehicle group. TFA also showed a significant (p < 0.05) diminished in paw edema and complete recovered of the edema after 5 days of treatment indicating the anti-inflammatory effects. However, TFA with ETO notably diminished the anti-inflammatory effects of ETO by enhancing paw edema diameter and licking number. TFA also expressed elevated binding affinity of -7.5 and -6.5 kcal/mol toward nitric oxide (NO) synthase and COX-1, respectively. In conclusion, TFA exerted anti-inflammatory effects and reduces anti-inflammatory capability of ETO.
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Affiliation(s)
- Md Shimul Bhuia
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
- BioLuster Research Center Ltd., Gopalganj, Bangladesh
| | - Raihan Chowdhury
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
- BioLuster Research Center Ltd., Gopalganj, Bangladesh
| | - Rubel Hasan
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
- BioLuster Research Center Ltd., Gopalganj, Bangladesh
| | - Md Sakib Al Hasan
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
| | - Siddique Akber Ansari
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Irfan Aamer Ansari
- Department of Drug Science and Technology, University of Turin, Turin, Italy
| | - Mohammad S Mubarak
- Department of Chemistry, The University of Jordan, Amman, Jordan
- Department of Chemistry, Indiana University, Bloomington, Indiana, USA
| | | | | | - Muhammad Torequl Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
- BioLuster Research Center Ltd., Gopalganj, Bangladesh
- Pharmacy Discipline, Khulna University, Khulna, Bangladesh
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Sindi AS, Stinson LF, Lai CT, Gridneva Z, Leghi GE, Netting MJ, Wlodek ME, Muhlhausler BS, Zhou X, Payne MS, Geddes DT. Human milk lactoferrin and lysozyme concentrations vary in response to a dietary intervention. J Nutr Biochem 2025; 135:109760. [PMID: 39251146 DOI: 10.1016/j.jnutbio.2024.109760] [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: 01/23/2024] [Revised: 08/08/2024] [Accepted: 09/04/2024] [Indexed: 09/11/2024]
Abstract
It is known that human milk (HM)1 antimicrobial protein composition varies during lactation. However, the impact of maternal diet on these antimicrobial proteins, particularly lactoferrin and lysozyme remains unknown. In addition, it is unclear whether daily, circadian, and between breast variations exist for lactoferrin and lysozyme concentrations. We investigated the impact of a low sugar, low fat, high fibre dietary intervention on HM lysozyme and lactoferrin concentrations. HM was sampled across a 3-week period; daily, at different times of day, and from both breasts to measure the level of intraindividual variation. The intervention significantly reduced maternal sugar, total fat, and saturated fat intake. HM lactoferrin concentration declined significantly over the course of the intervention however the effect size was relatively small. In addition, lactoferrin and lysozyme concentrations were variable over time, and differed significantly within and across the day but not between breasts.
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Affiliation(s)
- Azhar S Sindi
- Division of Obstetrics and Gynaecology, School of Medicine, The University of Western Australia, Subiaco, Western Australia, Australia; College of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; ABREAST Network, Perth, Western Australia, Australia; UWA Centre for Human Lactation Research and Translation, Crawley, Western Australia, Australia
| | - Lisa F Stinson
- ABREAST Network, Perth, Western Australia, Australia; UWA Centre for Human Lactation Research and Translation, Crawley, Western Australia, Australia; School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia
| | - Ching Tat Lai
- ABREAST Network, Perth, Western Australia, Australia; UWA Centre for Human Lactation Research and Translation, Crawley, Western Australia, Australia; School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia
| | - Zoya Gridneva
- ABREAST Network, Perth, Western Australia, Australia; UWA Centre for Human Lactation Research and Translation, Crawley, Western Australia, Australia; School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia
| | - Gabriela E Leghi
- School of Agriculture, Food and Wine, The University of Adelaide, Urrbrae, South Australia, Australia
| | - Merryn J Netting
- Women and Kids Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, South Australia, Australia; Discipline of Paediatrics, The University of Adelaide, North Adelaide, South Australia, Australia; Women's and Children's Hospital, North Adelaide, South Australia, Australia
| | - Mary E Wlodek
- School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
| | - Beverly S Muhlhausler
- School of Agriculture, Food and Wine, The University of Adelaide, Urrbrae, South Australia, Australia; CSIRO, Adelaide, South Australia, Australia
| | - Xiaojie Zhou
- ABREAST Network, Perth, Western Australia, Australia; UWA Centre for Human Lactation Research and Translation, Crawley, Western Australia, Australia; School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia
| | - Matthew S Payne
- Division of Obstetrics and Gynaecology, School of Medicine, The University of Western Australia, Subiaco, Western Australia, Australia
| | - Donna T Geddes
- ABREAST Network, Perth, Western Australia, Australia; UWA Centre for Human Lactation Research and Translation, Crawley, Western Australia, Australia; School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
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Smolińska K, Hułas-Stasiak M, Dobrowolska K, Sobczyński J, Szopa A, Tomaszewska E, Muszyński S, Smoliński K, Dobrowolski P. Effects of an Innovative High-Fat Diet on Intestinal Structure, Barrier Integrity, and Inflammation in a Zebrafish Model of Visceral Obesity. Int J Mol Sci 2024; 25:12723. [PMID: 39684433 DOI: 10.3390/ijms252312723] [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: 10/20/2024] [Revised: 11/13/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
High-fat diet (HFD)-induced obesity is a global health concern associated with gastrointestinal disorders. While mammalian models have elucidated the effects of a HFD on intestinal structure and function, its impact on zebrafish, a crucial model for studying diet-induced obesity and gastrointestinal dysfunction, remains inadequately characterized. This study investigated the influence of a HFD on zebrafish intestinal morphology, tight junction (TJ) protein expression, and inflammatory markers. Zebrafish fed a control diet or HFD with 40% or 60% fat exhibited significant alterations in intestinal morphology, with increased villi number but reduced villi width and length, suggesting compensatory responses to dietary stress. TJ protein expression (Claudin 2, Claudin 3, and Claudin 10) showed complex changes, particularly in the HFD60 juvenile group, indicating a multifaceted response in barrier integrity. Pro-inflammatory cytokine IL-6 and TNF-α levels were lower in both the juvenile and adult HFD60 groups than in the HFD40 and control groups, while elevated anti-inflammatory IL-10 levels in HFD60 adult zebrafish suggested activation of compensatory mechanisms. These findings highlight zebrafish as a valuable model for studying the effects of HFD on intestinal health and provide insights into the relationship between dietary fat, gut dysfunction, and inflammation.
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Affiliation(s)
- Katarzyna Smolińska
- Chronic Wounds Laboratory, Medical University of Lublin, Chodźki St. 7, 20-093 Lublin, Poland
| | - Monika Hułas-Stasiak
- Department of Functional Anatomy and Cytobiology, Maria Curie Sklodowska University, Akademicka St. 19, 20-033 Lublin, Poland
| | - Katarzyna Dobrowolska
- Faculty of Biology and Biotechnology, Maria Curie Sklodowska University, Akademicka St. 19, 20-033 Lublin, Poland
| | - Jan Sobczyński
- Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, Chodźki St. 7, 20-093 Lublin, Poland
| | - Aleksandra Szopa
- Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, Chodźki St. 7, 20-093 Lublin, Poland
| | - Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950 Lublin, Poland
| | - Siemowit Muszyński
- Department of Biophysics, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland
| | - Kacper Smoliński
- Faculty of Biology, Warsaw University, Żwirki i Wigury St. 101, 02-089 Warsaw, Poland
| | - Piotr Dobrowolski
- Department of Functional Anatomy and Cytobiology, Maria Curie Sklodowska University, Akademicka St. 19, 20-033 Lublin, Poland
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Mohaghegh N, Ahari A, Buttles C, Davani S, Hoang H, Huang Q, Huang Y, Hosseinpour B, Abbasgholizadeh R, Cottingham AL, Farhadi N, Akbari M, Kang H, Khademhosseini A, Jucaud V, Pearson RM, Hassani Najafabadi A. Simvastatin-Loaded Polymeric Nanoparticles: Targeting Inflammatory Macrophages for Local Adipose Tissue Browning in Obesity Treatment. ACS NANO 2024; 18:27764-27781. [PMID: 39342648 DOI: 10.1021/acsnano.4c10742] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/01/2024]
Abstract
Obesity is defined as chronic, low-grade inflammation within specific tissues. Given the escalating prevalence of obesity among individuals of all ages, obesity has reached epidemic proportions, posing an important public health challenge. Despite significant advancements in treating obesity, conventional approaches remain largely ineffective or involve severe side effects, thus underscoring the pressing need to explore and develop treatment approaches. Targeted and local immunomodulation using nanoparticles (NPs) can influence fat production and utilization processes. Statins, known for their anti-inflammatory properties, show the potential for mitigating obesity-related inflammation. A localized delivery option offers several advantages over oral and parenteral delivery methods. Here, we developed simvastatin (Sim) encapsulated within PLGA NPs (Sim-NP) for localized delivery of Sim to adipose tissues (ATs) for immunomodulation to treat obesity. In vitro experiments revealed the strong anti-inflammatory effects of Sim-NPs, which resulted in enhanced modulation of macrophage (MΦ) polarization and induction of AT browning. We then extended our investigation to an in vivo mouse model of high-fat-diet (HFD)-induced obesity. Sim-NP administration led to the controlled release of Sim within AT, directly impacting MΦ activity and inducing AT browning while inducing weight loss. Our findings demonstrated that Sim-NP administration effectively inhibited the progression of obesity-related inflammation, controlled white fat production, and enhanced AT modulation. These results highlight the potential of Sim-NP as a potent nanotherapy for treating obesity by modulating the immune system.
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Affiliation(s)
- Neda Mohaghegh
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
| | - Amir Ahari
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
- Department of Surgery, University of California-Los Angeles, Los Angeles, California 90095, United States
| | - Claire Buttles
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
- Department of Biology, Indiana University Bloomington, Bloomington, Indiana 47405, United States
| | - Saya Davani
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
- Department of Neurobiology, Physiology, and Behavior, University of California Davis, Briggs Hall, Davis, California 95616, United States
| | - Hanna Hoang
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
- Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90024, United States
| | - Qiang Huang
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
| | - Yixuan Huang
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
| | - Bahareh Hosseinpour
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
- Department of Chemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada
| | - Reza Abbasgholizadeh
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
| | - Andrea L Cottingham
- Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States
| | - Neda Farhadi
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
| | - Mohsen Akbari
- Department of Mechanical Engineering, University of Victoria, Victoria, British Columbia V8P 5C2, Canada
- Biotechnology Center, Silesian University of Technology, Gliwice 44-100, Poland
| | - Heemin Kang
- Department of Materials Science and Engineering, Korea University, Seoul 02841, Republic of Korea
| | - Ali Khademhosseini
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
| | - Vadim Jucaud
- Terasaki Institute for Biomedical Innovation, Los Angeles, California 90064, United States
| | - Ryan M Pearson
- Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States
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Kim N, Shin HY. Deciphering the Potential Role of Specialized Pro-Resolving Mediators in Obesity-Associated Metabolic Disorders. Int J Mol Sci 2024; 25:9598. [PMID: 39273541 PMCID: PMC11395256 DOI: 10.3390/ijms25179598] [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: 08/23/2024] [Revised: 09/02/2024] [Accepted: 09/03/2024] [Indexed: 09/15/2024] Open
Abstract
Obesity-related metabolic disorders, including diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease, increasingly threaten global health. Uncontrolled inflammation is a key pathophysiological factor in many of these conditions. In the human body, inflammatory responses generate specialized pro-resolving mediators (SPMs), which are crucial for resolving inflammation and restoring tissue balance. SPMs derived from omega-3 polyunsaturated fatty acids (n-3 PUFAs) such as resolvins, protectins, and maresins hold promise in attenuating the chronic inflammatory diseases associated with lipid metabolism disorders. Recent research has highlighted the therapeutic potential of n-3 PUFA-derived metabolites in addressing these metabolic disorders. However, the understanding of the pharmacological aspects of SPMs, particularly in obesity-related metabolic disorders, remains limited. This review comprehensively summarizes recent advances in understanding the role of SPMs in resolving metabolic disorders, based on studies in animal models and humans. These studies indicate that SPMs have potential as therapeutic targets for combating obesity, as well as offering insights into their mechanisms of action.
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Affiliation(s)
- Nahyun Kim
- Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea
| | - Ha Youn Shin
- Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea
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McKechnie T, Ramji K, Saddik M, Leitch J, Farooq A, Patel S, Doumouras A, Parpia S, Eskicioglu C, Bhandari M. PReoperative very low-Energy diets for obese PAtients undergoing non-bariatric surgery Randomized Evaluation (PREPARE): a protocol for a pilot randomized controlled trial. Pilot Feasibility Stud 2024; 10:82. [PMID: 38773543 PMCID: PMC11106982 DOI: 10.1186/s40814-024-01511-6] [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: 09/18/2023] [Accepted: 05/14/2024] [Indexed: 05/24/2024] Open
Abstract
BACKGROUND Patients with obesity presenting in need of surgical intervention are at 2-to-sixfold higher risk of prolonged hospitalization, infectious morbidity, venous thromboembolism, and more. To mitigate some of these concerns, prescribed preoperative weight loss via very low-energy diets (VLEDs) has become a standard of care for patients with obesity undergoing bariatric surgery. While VLEDs have become standard prior to bariatric surgery, their application in other surgical settings remains limited. A large, definitive trial is required to resolve the uncertainty surrounding their use in these patients. Prior to a definitive trial to compare the efficacy of VLEDs in patients with obesity undergoing major non-bariatric surgery, we require a pilot trial. We argue a pilot trial will provide the following critical feasibility insights: (1) assessment of recruitment ability, (2) evaluation of adherence to VLED regimens, and (3) assessment of our ability follow patients completely. METHODS The proposed trial will be a multi-center, surgeon, outcome assessor, and data-analyst blinded, parallel pilot randomized controlled trial (RCT). Patients older than 18 years of age with a body mass index (BMI) of greater than 30 kg/m2 undergoing major elective non-bariatric surgery will be eligible for inclusion. Consecutive patients will be allocated 1:1 according to a computer-generated randomization schedule. Randomization will be stratified by center and will employ randomly permutated blocks. All patients in the intervention group will receive standard patient counseling on weight loss and an active VLED protocol. The preoperative VLED protocol will utilize commercially available weight loss products for three weeks preoperatively. The primary outcomes (randomization percentage, recruitment rate, intervention adherence, follow-up completion, network development) will assess feasibility. Descriptive statistics will be used to characterize the study sample. DISCUSSION The PREPARE pilot RCT will aim to provide feasibility and safety data that will allow for the successful completion of the definitive PREPARE trial that has the potential to provide practice changing data pertaining to the regular use of VLEDs as a means of pre-habilitation for patients with obesity undergoing major non-bariatric surgery. TRIAL REGISTRATION This study was registered on ClinicalTrials.gov (reference #NCT05918471) on June 23, 2023.
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Affiliation(s)
- Tyler McKechnie
- Department of Surgery, Division of General Surgery, McMaster University, 1280 Main St. W, Hamilton, ON, L8S 4L8, Canada.
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
| | - Karim Ramji
- Department of Surgery, Division of General Surgery, McMaster University, 1280 Main St. W, Hamilton, ON, L8S 4L8, Canada
- Department of Surgery, Division of General Surgery, St. Joseph Healthcare, Hamilton, ON, Canada
| | - Maisa Saddik
- Department of Surgery, Division of General Surgery, McMaster University, 1280 Main St. W, Hamilton, ON, L8S 4L8, Canada
| | - Jordan Leitch
- Department of Anesthesia and Perioperative Medicine, Queen's University, Kingston Health Sciences Centre, Kingston, ON, Canada
| | - Ameer Farooq
- Department of Surgery, Division of General Surgery, Queen's University, Kingston Health Sciences Centre, Kingston, ON, Canada
| | - Sunil Patel
- Department of Surgery, Division of General Surgery, Queen's University, Kingston Health Sciences Centre, Kingston, ON, Canada
| | - Aristithes Doumouras
- Department of Surgery, Division of General Surgery, McMaster University, 1280 Main St. W, Hamilton, ON, L8S 4L8, Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
- Department of Surgery, Division of General Surgery, St. Joseph Healthcare, Hamilton, ON, Canada
| | - Sameer Parpia
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
- Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Cagla Eskicioglu
- Department of Surgery, Division of General Surgery, McMaster University, 1280 Main St. W, Hamilton, ON, L8S 4L8, Canada
- Department of Surgery, Division of General Surgery, St. Joseph Healthcare, Hamilton, ON, Canada
| | - Mohit Bhandari
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
- Department of Surgery, Division of Orthopedic Surgery, McMaster University, Hamilton, ON, Canada
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Acciarino A, Diwakarla S, Handreck J, Bergola C, Sahakian L, McQuade RM. The role of the gastrointestinal barrier in obesity-associated systemic inflammation. Obes Rev 2024; 25:e13673. [PMID: 38111141 DOI: 10.1111/obr.13673] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 10/05/2023] [Accepted: 10/27/2023] [Indexed: 12/20/2023]
Abstract
Systemic inflammation is a key contributor to the onset and progression of several obesity-associated diseases and is thought to predominantly arise from the hyperplasia and hypertrophy of white adipose tissue. However, a growing body of works suggests that early changes in the gastrointestinal (GI) barrier may contribute to both local, within the GI lining, and systemic inflammation in obesity. Intestinal barrier dysfunction is well-characterized in inflammatory GI disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and is known to contribute to systemic inflammation. Thus, drawing parallels between GI disorders, where intestinal permeability and systemic inflammation are prominent features, and obesity-induced GI manifestations may provide insights into the potential role of the intestinal barrier in systemic inflammation in obesity. This review summarizes the current literature surrounding intestinal barrier dysfunction in obesity and explores the potential role of intestinal hyperpermeability and intestinal barrier dysfunction in the development of systemic inflammation and GI dysfunction in obesity.
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Affiliation(s)
- Adriana Acciarino
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Shanti Diwakarla
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Jessica Handreck
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Cedrick Bergola
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Lauren Sahakian
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Rachel M McQuade
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
- Australian Institute for Musculoskeletal Science (AIMSS), Melbourne University, Melbourne, Victoria, Australia
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10
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Hardiany NS, Dewi PKK, Dewi S, Tejo BA. Exploration of neuroprotective effect from Coriandrum sativum L. ethanolic seeds extracts on brain of obese rats. Sci Rep 2024; 14:603. [PMID: 38182767 PMCID: PMC10770154 DOI: 10.1038/s41598-024-51221-5] [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: 11/06/2023] [Accepted: 01/02/2024] [Indexed: 01/07/2024] Open
Abstract
In this study, the potential neuroprotective ability of coriander seeds (Coriandrum sativum L.) ethanolic extract (CSES) as a neuroprotectant agent in the brains of high-fat diet-induced obese rats was analyzed. The study investigated how CSES impacts oxidative stress markers (i.e., malondialdehyde/MDA, glutathione/GSH and catalase), inflammation marker (i.e., Interleukin-6/IL-6), cellular senescence markers (i.e., senescence-associated β-galactoside/SA-β-Gal activity and p16), brain damage marker (i.e., Neuron-specific Enolase/NSE), and neurogenesis markers (i.e., mature Brain-derived Neurotropic Factor/BDNF, pro-BDNF, and mature/pro-BDNF ratio). Male adult Wistar rats were fed a high-fat diet and given CSES once daily, at 100 mg/kg body weight, for 12 weeks. CSES significantly reduced MDA concentration (p = < 0.001), SA-β-Gal activity (p = 0.010), and increased GSH concentration (p = 0.047) in the brain of obese rats; however, the decrease of IL-6, NSE, and p16 as well as the increase of catalase specific activity and BDNF expression were not significant. Moreover, the mature/pro-BDNF ratio was significantly higher in the brains of non-obese rats, both given the control diet and the high-fat diet compared to the control. Our results suggest that obese rats benefited from consuming CSES, showing improved oxidative stress levels, reduced cellular senescence and increased endogenous antioxidants, making CSES a potential neuroprotective agent.
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Affiliation(s)
- Novi Silvia Hardiany
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia.
- Center of Hypoxia and Oxidative Stress Studies, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia.
| | - Putri Krishna Kumara Dewi
- Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia
- Medical Biochemistry Division, Department of Biomedical Science, Faculty of Medicine, Universitas Pendidikan Ganesha, Bali, 81116, Indonesia
| | - Syarifah Dewi
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia
- Center of Hypoxia and Oxidative Stress Studies, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia
| | - Bimo A Tejo
- Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400, Serdang, Malaysia
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Shalchian Z, Taheri S, Hafezi M, Madani T, Nasiri N, Eftekhari Yazdi P. Embryo Condition Media Collected from Polycystic Ovary Syndrome Patients with Abdominal Obesity Can Increase The Decidualization Potential of Healthy Endometrial Stromal Cells. INTERNATIONAL JOURNAL OF FERTILITY & STERILITY 2023; 18:67-75. [PMID: 38041462 PMCID: PMC10692747 DOI: 10.22074/ijfs.2023.2006784.1491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/17/2023] [Accepted: 09/23/2023] [Indexed: 12/03/2023]
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is a common endocrinological disorder associated with abdominal obesity (AO) and some reproductive complications including low pregnancy rate. Embryo-endometrium cross-talk has a key role in successful embryo implantation and subsequent normal pregnancy rate. The primary objective of this study is to evaluate the decidualization potential of endometrial stromal cells (ESCs) using the embryo condition media (ECM) collected from PCOS patients with AO, compared to ECM of those patients without AO. MATERIALS AND METHODS In this experimental study, we measured the capacity of ECM collected from PCOS patients with or without AO for decidualization induction in healthy ESCs after coculture. A total number of 53 embryos from 40 couples belonging to PCOS with AO, PCOS without AO, nonPCOS with AO, and nonPCOS without AO patients, were included in our study. The embryosof four groups were single-cultured up to the blastocyst stage. Their ECM (45λ/well) were pooled and added to healthy ESCs monolayer culture media to investigate their effects on decidualization potential via gene (PRL, IGFBP1, IL1-β, HOXA10, IL-6 and TNF-α) and protein (PRL, IGFBP1, IL1-β) expression analysis and ESCs migration assay. RESULTS The morphological analysis, migration assay (P≤0.0321), protein (P≤0.0139) and gene expression analysis showed PCOS with AO accounted for the highest gene (PRL, IGFBP1, IL1-β, HOXA10, IL-6, TNF-α) and protein markers (PRL, IGFBP1, IL1-β) (P≤0.05). NonPCOS individuals without AO had the lowest level of both gene and protein decidualization markers (P≤0.05). CONCLUSION Considering decidualization as an inflammatory process, a higher level of decidualization markers was associated with a higher inflammatory status created by AO and PCOS, separately. Inflammation may disrupt the process of inflammatory to anti-inflammatory phase required for prevention of pregnancy loss, this could explain the high rate of abortion in these cases.
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Affiliation(s)
- Zohreh Shalchian
- Faculty of Development of Biology, University of Science and Culture, Tehran, Iran
| | - Saba Taheri
- Faculty of Development of Biology, University of Science and Culture, Tehran, Iran
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Maryam Hafezi
- Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Tahereh Madani
- Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Nahid Nasiri
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
- Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute Academic Center for Education, Culture and Research (ACECR), Tehran, Iran
| | - Poopak Eftekhari Yazdi
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
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Sachan A, Aggarwal S, Pol MM, Singh A, Yadav R. Expression analysis of MMP14: Key enzyme action in modulating visceral adipose tissue plasticity in patients with obesity. Clin Obes 2023; 13:e12607. [PMID: 37340990 DOI: 10.1111/cob.12607] [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: 08/23/2022] [Revised: 05/03/2023] [Accepted: 05/30/2023] [Indexed: 06/22/2023]
Abstract
Compromised adipose tissue plasticity is a hallmark finding of obesity orchestrated by the intricate interplay between various extracellular matrix components. Collagen6 (COL6) is well characterized in obese visceral adipose tissue (VAT), not much is known about MMP14 which is hypothesized to be the key player in matrix reorganization. Subjects with obesity (BMI ≥40; n = 50) aged 18-60 years undergoing bariatric surgery and their age-matched controls (BMI < 25; n = 30) were included. MMP14, Col6A3 and Tissue inhibitor of metalloproteinase 2 (TIMP2) mRNA expression was assessed in VAT and their serum levels along with endotrophin were estimated in both groups preoperatively and post-operatively in the obese group. The results were analysed statistically and correlated with anthropometric and glycaemic parameters, namely fasting glucose and insulin, HbA1c, HOMA-IR, HOMA-β and QUICKI. Circulating levels as well as mRNA expression profiling revealed significant differences between the individuals with and without obesity (p < .05), more so in individuals with diabetes and obesity (p < .05). Follow-up serum analysis revealed significantly raised MMP14 (p < .001), with decreased Col6A3, endotrophin and TIMP2 levels (p < .01, p < .001 and p < .01, respectively). A rise in serum MMP14 protein, simultaneous with post-surgical weight loss and decreased serum levels of associated extracellular matrix (ECM) remodellers, suggests its crucial role in modulating obesity-associated ECM fibrosis and pliability of VAT.
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Affiliation(s)
- Astha Sachan
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Aggarwal
- Department of Surgical Disciplines, CMET, All India Institute of Medical Sciences, New Delhi, India
| | - Manjunath Maruti Pol
- Department of Surgical Disciplines, CMET, All India Institute of Medical Sciences, New Delhi, India
| | - Archna Singh
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Rakhee Yadav
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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Bahari H, Rafiei H, Goudarzi K, Omidian K, Asbaghi O, Kolbadi KSH, Naderian M, Hosseini A. The effects of pomegranate consumption on inflammatory and oxidative stress biomarkers in adults: a systematic review and meta-analysis. Inflammopharmacology 2023; 31:2283-2301. [PMID: 37507609 DOI: 10.1007/s10787-023-01294-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023]
Abstract
BACKGROUND Several studies have shown the effects of pomegranate on oxidative stress and inflammation biomarkers, while some studies showed no effects of pomegranate on these biomarkers. Therefore, we aimed to evaluate the effects of pomegranate consumption on C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor α (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in adults. METHODS A systematic literature search was performed using databases, including PubMed, Web of Science, and Scopus, up to May 2023 to identify eligible randomized controlled trials (RCTs). Heterogeneity tests of the included trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. RESULTS Of 3811 records, 33 eligible RCTs were included in the current study. Our meta-analysis of the pooled findings showed that pomegranate consumption significantly reduced CRP (WMD: -0.50 mg/l; 95% CI -0.79 to -0.20; p = 0.001), IL-6 (WMD: -1.24 ng/L 95% CI -1.95 to -0.54; p = 0.001), TNF-α (WMD: -1.96 pg/ml 95%CI -2.75 to -1.18; p < 0.001), and MDA (WMD: -0.34 nmol/ml 95%CI -0.42 to -0.25; p < 0.001). Pooled analysis of 13 trials revealed that pomegranate consumption led to a significant increase in TAC (WMD: 0.26 mmol/L 95%CI 0.03 to 0.49; p = 0.025). CONCLUSION Overall, the results demonstrated that pomegranate consumption has beneficial effects on oxidative stress and inflammatory biomarkers in adults. Therefore, pomegranate can be consumed as an effective dietary approach to attenuate oxidative stress and inflammation in patients with cardiovascular diseases. PROSPERO REGISTRATION CODE CRD42023406684.
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Affiliation(s)
- Hossein Bahari
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Rafiei
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - Kian Goudarzi
- Faculty of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Kosar Omidian
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - Omid Asbaghi
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Moslem Naderian
- Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Ali Hosseini
- Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
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Chen AK, Gullett JM, Williamson JB, Cohen RA. Presurgical microstructural coherence predicts cognitive change for bariatric surgery patients. Obesity (Silver Spring) 2023; 31:2325-2334. [PMID: 37605633 PMCID: PMC10449364 DOI: 10.1002/oby.23837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 04/20/2023] [Accepted: 05/17/2023] [Indexed: 08/23/2023]
Abstract
OBJECTIVE This observational study examined the relationship between presurgical white matter microstructural coherence and cognitive change after weight loss. It was hypothesized that higher baseline fractional anisotropy (FA) would predict greater baseline and change cognition. METHODS A sample of 24 adults (BMI ≥ 35 kg/m2 ) underwent neuropsychological assessment at baseline and 12 weeks after bariatric surgery. A magnetic resonance imaging brain scan was administered at baseline and processed through Tract-Based Spatial Statistics to compute FA in white matter tracts of interest. Composite scores for attention, learning, processing speed, executive function, verbal fluency, working memory, and overall cognition were calculated. RESULTS As expected, FA in some tracts of interest was significantly (p < 0.05) positively associated with change in cognition. Inverse relationships were observed between baseline FA and presurgical cognition, which may be explained by increased medial and radial diffusivity and preserved axonal diffusivity. Cognition generally improved after surgery; however, relative but clinically nonsignificant deterioration was observed on learning measures. Poorer baseline cognitive performance was associated with greater postsurgical cognitive improvement. CONCLUSIONS Presurgical microstructural coherence is associated with magnitude of cognitive change after weight loss. An observed reduction in learning suggests that bariatric surgery may lead to negative outcomes in some cognitive domains, at least temporarily.
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Affiliation(s)
- Alexa K Chen
- Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA
| | - Joseph M Gullett
- Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA
| | - John B Williamson
- Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA
| | - Ronald A Cohen
- Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA
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McKechnie T, Lee Y, Dionne J, Doumouras A, Parpia S, Bhandari M, Eskicioglu C. Very low energy diets prior to bariatric surgery may reduce postoperative morbidity: a systematic review and meta-analysis of randomized controlled trials. Front Nutr 2023; 10:1211575. [PMID: 37408988 PMCID: PMC10319356 DOI: 10.3389/fnut.2023.1211575] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 05/23/2023] [Indexed: 07/07/2023] Open
Abstract
Purpose To optimize patients prior to bariatric surgery, very low energy diets (VLEDs) are often employed for 2-4 weeks preoperatively. They are known to result in preoperative weight loss, decrease liver volume, and decrease surgeon-perceived operative difficulty. Their impact on postoperative morbidity has been less extensively studied. We performed a focused systematic review and meta-analysis with the aim of comparing preoperative VLEDs prior to bariatric surgery with controls in terms of overall postoperative morbidity. Methods MEDLINE, Embase, and CENTRAL were searched from database inception to February 2023. Articles were eligible for inclusion if they were randomized controlled trials (RCTs) comparing postoperative morbidity in adult patients (i.e., over the age of 18) receiving a VLED with liquid formulation to those receiving a non-VLED control prior to elective bariatric surgery. Outcomes included overall 30-day postoperative morbidity and preoperative weight loss. An inverse variance meta-analysis was performed with GRADE assessment of the quality of evidence. Results After reviewing 2,525 citations, four RCTs with 294 patients receiving preoperative VLEDs with liquid formulation and 294 patients receiving a non-VLED control met inclusion. Patients receiving VLED experienced significantly more preoperative weight loss than patients receiving control (mean difference (MD) 3.38 kg, 95% confidence interval (CI) 1.06-5.70, p = 0.004, I2 = 95%). According to low certainty evidence, there was a non-significant reduction in 30-day postoperative morbidity in patients receiving VLED prior to bariatric surgery (risk ratio (RR) 0.67, 95%CI 0.39-1.17, p = 0.16, I2 = 0%). Conclusion The impact of preoperative VLEDs on postoperative outcomes following bariatric surgery remains unclear. It is possible that VLEDs may contribute to decreased postoperative morbidity, but further larger prospective trials are required to investigate the signal identified in this study.
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Affiliation(s)
- Tyler McKechnie
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - Yung Lee
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, United States
| | - Joanna Dionne
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - Aristithes Doumouras
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
- Division of General Surgery, Department of Surgery, St. Joseph Healthcare, Hamilton, ON, Canada
| | - Sameer Parpia
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - Mohit Bhandari
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
- Division of Orthopedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Cagla Eskicioglu
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
- Division of General Surgery, Department of Surgery, St. Joseph Healthcare, Hamilton, ON, Canada
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Tang C, Zhou R, Cao K, Liu J, Kan J, Qian C, Jin C. Current progress in the hypoglycemic mechanisms of natural polysaccharides. Food Funct 2023; 14:4490-4506. [PMID: 37083079 DOI: 10.1039/d3fo00991b] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/22/2023]
Abstract
Unhealthy dietary pattern-induced type 2 diabetes mellitus poses a great threat to human health all over the world. Accumulating evidence has revealed that the pathophysiology of type 2 diabetes mellitus is closely associated with the dysregulation of glucose metabolism and energy metabolism, serious oxidative stress, prolonged endoplasmic reticulum stress, metabolic inflammation and intestinal microbial dysbiosis. Most important of all, insulin resistance and insulin deficiency are two key factors inducing type 2 diabetes mellitus. Nowadays, natural polysaccharides have gained increasing attention owing to their numerous health-promoting functions, such as hypoglycemic, energy-regulating, antioxidant, anti-inflammatory and prebiotic activities. Therefore, natural polysaccharides have been used to alleviate diet-induced type 2 diabetes mellitus. Specifically, this review comprehensively summarizes the underlying hypoglycemic mechanisms of natural polysaccharides and provides a theoretical basis for the development of functional foods. For the first time, this review elucidates hypoglycemic mechanisms of natural polysaccharides from the perspectives of their regulatory effects on glucose metabolism, insulin resistance and mitochondrial dysfunction.
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Affiliation(s)
- Chao Tang
- College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, Jiangsu, China.
| | - Ruizheng Zhou
- Dongguan Institutes For Food and Drug Control, Dongguan 523808, Guangdong, China
| | - Kexin Cao
- College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, Jiangsu, China.
| | - Jun Liu
- College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, Jiangsu, China.
| | - Juan Kan
- College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, Jiangsu, China.
| | - Chunlu Qian
- College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, Jiangsu, China.
| | - Changhai Jin
- College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, Jiangsu, China.
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Yang J, Liang C, Liu L, Wang L, Yu G. High-Fat Diet Related Lung Fibrosis-Epigenetic Regulation Matters. Biomolecules 2023; 13:biom13030558. [PMID: 36979493 PMCID: PMC10046645 DOI: 10.3390/biom13030558] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/12/2023] [Accepted: 03/16/2023] [Indexed: 03/30/2023] Open
Abstract
Pulmonary fibrosis (PF) is an interstitial lung disease characterized by the destruction of the pulmonary parenchyma caused by excessive extracellular matrix deposition. Despite the well-known etiological factors such as senescence, aberrant epithelial cell and fibroblast activation, and chronic inflammation, PF has recently been recognized as a metabolic disease and abnormal lipid signature was observed both in serum and bronchoalveolar lavage fluid (BALF) of PF patients and mice PF model. Clinically, observational studies suggest a significant link between high-fat diet (HFD) and PF as manifested by high intake of saturated fatty acids (SFAs) and meat increases the risk of PF and mice lung fibrosis. However, the possible mechanisms between HFD and PF remain unclear. In the current review we emphasize the diversity effects of the epigenetic dysregulation induced by HFD on the fibrotic factors such as epithelial cell injury, abnormal fibroblast activation and chronic inflammation. Finally, we discuss the potential ways for patients to improve their conditions and emphasize the prospect of targeted therapy based on epigenetic regulation for scientific researchers or drug developers.
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Affiliation(s)
- Juntang Yang
- State Key Laboratory of Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, China
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, Henan Normal University, Xinxiang 453007, China
| | - Chenxi Liang
- State Key Laboratory of Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, China
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, Henan Normal University, Xinxiang 453007, China
| | - Lulu Liu
- State Key Laboratory of Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, China
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, Henan Normal University, Xinxiang 453007, China
| | - Lan Wang
- State Key Laboratory of Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, China
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, Henan Normal University, Xinxiang 453007, China
| | - Guoying Yu
- State Key Laboratory of Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, China
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, Henan Normal University, Xinxiang 453007, China
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Čolak D, Cmok Kučič A, Pintar T, Gašperšič R. Periodontal Therapy in Bariatric Surgery Patients with Periodontitis: Randomized Control Clinical Trial. J Clin Med 2022; 11:6837. [PMID: 36431314 PMCID: PMC9693218 DOI: 10.3390/jcm11226837] [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: 10/28/2022] [Revised: 11/15/2022] [Accepted: 11/17/2022] [Indexed: 11/22/2022] Open
Abstract
Background: Bariatric surgery (BS) patients may experience the progression of periodontitis during recovery. We aimed to determine whether non-surgical periodontal therapy before BS improves the periodontal and systemic health parameters after the surgery. Methods: BS candidates with periodontitis were randomized into the test (TG) and control group (CG). One month before BS (pre-BS), patients in the TG (n = 15) received non-surgical periodontal therapy, while patients in the CG (n = 15) received only mechanical plaque removal. Patients were re-examined 3 and 6 months after BS. Differences between the TG and CG in clinical periodontal parameters, systemic health-related serum biomarkers, parameters of obesity, and prevalence of obesity-related diseases were evaluated. Results: From the 30 included patients, 26 were re-examined at 3 months and 20 patients at 6 months. Periodontal parameters bleeding on probing (p = 0.015), periodontal pocket dept (PPD, p = 0.0015), % PPD > 4 mm (p < 0.001), and full-mouth plaque levels (p = 0.002) were lower in the TG than in the CG at 6 months after BS. There is a general improvement in systemic health after BS without significant differences (p > 0.05) between the TG and CG at the 6-month follow-up. The TG shows a tendency for improvement in metabolic syndrome components at the 6-month follow-up compared to pre-BS (p < 0.05). Conclusions: Non-surgical periodontal therapy in periodontitis patients before the BS may improve periodontal health 3 and 6 months after the surgery. The possible benefits of periodontal therapy on the overall health of BS patients should be further explored.
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Affiliation(s)
- Dejana Čolak
- Department of Oral Diseases and Periodontology, Dental Clinic, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Alja Cmok Kučič
- Department of Oral Diseases and Periodontology, Dental Clinic, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Tadeja Pintar
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Abdominal Surgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Rok Gašperšič
- Department of Oral Diseases and Periodontology, Dental Clinic, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
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Toba-Oluboka T, Vochosková K, Hajek T. Are the antidepressant effects of insulin-sensitizing medications related to improvements in metabolic markers? Transl Psychiatry 2022; 12:469. [PMID: 36347837 PMCID: PMC9643486 DOI: 10.1038/s41398-022-02234-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 10/22/2022] [Accepted: 10/25/2022] [Indexed: 11/09/2022] Open
Abstract
Insulin-sensitizing medications were originally used in psychiatric practice to treat weight gain and other metabolic side effects that accompany the use of mood stabilizers, antipsychotics, and some antidepressants. However, in recent studies these medications have been shown to cause improvement in depressive symptoms, creating a potential new indication outside of metabolic regulation. However, it is still unclear whether the antidepressant properties of these medications are associated with improvements in metabolic markers. We performed a systematic search of the literature following PRISMA guidelines of studies investigating antidepressant effects of insulin-sensitizing medications. We specifically focused on whether any improvements in depressive symptoms were connected to the improvement of metabolic dysfunction. Majority of the studies included in this review reported significant improvement in depressive symptoms following treatment with insulin-sensitizing medications. Nine out of the fifteen included studies assessed for a correlation between improvement in symptoms and changes in metabolic markers and only two of the nine studies found such association, with effect sizes ranging from R2 = 0.26-0.38. The metabolic variables, which correlated with improvements in depressive symptoms included oral glucose tolerance test, fasting plasma glucose and glycosylated hemoglobin following treatment with pioglitazone or metformin. The use of insulin-sensitizing medications has a clear positive impact on depressive symptoms. However, it seems that the symptom improvement may be unrelated to improvement in metabolic markers or weight. It is unclear which additional mechanisms play a role in the observed clinical improvement. Some alternative options include inflammatory, neuroinflammatory changes, improvements in cognitive functioning or brain structure. Future studies of insulin-sensitizing medications should measure metabolic markers and study the links between changes in metabolic markers and changes in depression. Additionally, it is important to use novel outcomes in these studies, such as changes in cognitive functioning and to investigate not only acute, but also prophylactic treatment effects.
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Affiliation(s)
- Temi Toba-Oluboka
- grid.55602.340000 0004 1936 8200Department of Psychiatry, Dalhousie University, Halifax, NS Canada
| | - Kristýna Vochosková
- grid.447902.cNational Institute of Mental Health, Klecany, Czech Republic ,grid.4491.80000 0004 1937 116XCharles University, Third Faculty of Medicine, Prague, Czech Republic
| | - Tomas Hajek
- Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. .,National Institute of Mental Health, Klecany, Czech Republic.
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20
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Abdelmissih S. A Bitter Experience That Enlightens the Future: COVID-19 Neurological Affection and Perspectives on the Orexigenic System. Cureus 2022; 14:e30788. [DOI: 10.7759/cureus.30788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/27/2022] [Indexed: 11/06/2022] Open
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21
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Is Whole-Body Cryostimulation an Effective Add-On Treatment in Individuals with Fibromyalgia and Obesity? A Randomized Controlled Clinical Trial. J Clin Med 2022; 11:jcm11154324. [PMID: 35893415 PMCID: PMC9332222 DOI: 10.3390/jcm11154324] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 12/10/2022] Open
Abstract
Pain severity, depression, and sleep disturbances are key targets for FM rehabilitation. Recent evidence suggests that whole-body cryostimulation (WBC) might be an effective add-on treatment in the management of FM. The purpose of this study was to evaluate the effects of an add-on WBC intervention to a multidisciplinary rehabilitation program on pain intensity, depressive symptoms, disease impact, sleep quality, and performance-based physical functioning in a sample of FM patients with obesity. We performed a randomized controlled trial with 43 patients with FM and obesity undergoing a multidisciplinary rehabilitation program with and without the addition of ten 2-min WBC sessions at −110 °C over two weeks. According to our results, the implementation of ten sessions of WBC over two weeks produced additional benefits. Indeed, both groups reported positive changes after the rehabilitation; however, the group that underwent WBC intervention had greater improvements in the severity of pain, depressive symptoms, disease impact, and quality of sleep. On the contrary, with respect to performance-based physical functioning, we found no significant between-group differences. Our findings suggest that WBC could be a promising add-on treatment to improve key aspects of FM, such as pain, depressive symptoms, disease impact and poor sleep quality.
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22
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Sahin E, Saglam N, Erdem S, Alvuroglu E, Abidin I, Yulug E, Alver A. 7,8-Dihydroxyflavone alleviates Endoplasmic Reticulum Stress in cafeteria diet-induced metabolic syndrome. Life Sci 2022; 306:120781. [PMID: 35835252 DOI: 10.1016/j.lfs.2022.120781] [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: 06/17/2022] [Revised: 06/29/2022] [Accepted: 07/01/2022] [Indexed: 10/17/2022]
Abstract
AIMS Prolonged Endoplasmic Reticulum Stress (ERS) is involved in the pathogenesis of metabolic syndrome, including type-2 diabetes mellitus, cardiovascular diseases, atherosclerosis, obesity, and fatty liver disease. There have been significant efforts to discover molecules to treat ERS and/or to ameliorate associate symptoms. In this study, we investigated the effect of 7,8-Dihydroxyflavone (7,8-DHF) on ERS in liver and pancreas tissues in a cafeteria (CAF) diet induced metabolic syndrome model. MAIN METHODS Male C57BL/6 mice were fed CAF diet for 16 weeks and 7,8-DHF was administered intraperitoneally (5 mg/kg/day) for last four weeks. 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) in liver and pancreas tissues, insulin and interleukin-1β (IL-1β) in serum were analyzed by ELISA method and serum biochemistry parameters were analyzed with autoanalyzer. GRP78 and CHOP gene expression levels were determined by qRT-PCR. In addition, histopathological analyzes were performed on liver and pancreas tissues. KEY FINDINGS Findings revealed that CAF diet caused metabolic abnormalities, insulin resistance and inflammation in serum and triggered ERS in pancreas and liver tissues. 7,8-DHF treatment significantly reduced metabolic abnormalities by reducing serum biochemical parameters, HOMO-IR and IL-1β levels. qRT-PCR and ELISA results indicated that 7,8-DHF treatment down-regulated GRP78 and CHOP expression and protein levels in the liver and GRP78 expression in pancreas. Efficiency of 7,8-DHF in these tissues was also demonstrated by histopathological tests. SIGNIFICANCE In conclusion, CAF diet-induced metabolic syndrome model, 7,8-DHF suppressed ERS and ERS-induced metabolic disorders in both liver and pancreas. Therefore, 7,8-DHF may potentially be a novel therapeutic compound to ameliorate ERS and related metabolic symptoms.
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Affiliation(s)
- Elif Sahin
- Department of Medical Biochemistry, Graduate School of Medical Science, Karadeniz Technical University, Trabzon, Turkiye.
| | - Neslihan Saglam
- Department of Medical Biochemistry, Graduate School of Medical Science, Karadeniz Technical University, Trabzon, Turkiye
| | - Seniz Erdem
- Department of Medical Biochemistry, Graduate School of Medical Science, Karadeniz Technical University, Trabzon, Turkiye
| | - Elif Alvuroglu
- Department of Histology and Embryology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkiye
| | - Ismail Abidin
- Department of Biophysics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkiye
| | - Esin Yulug
- Department of Histology and Embryology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkiye
| | - Ahmet Alver
- Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkiye
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23
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Osorio-Conles Ó, Vega-Beyhart A, Ibarzabal A, Balibrea JM, Vidal J, de Hollanda A. Biological Determinants of Metabolic Syndrome in Visceral and Subcutaneous Adipose Tissue from Severely Obese Women. Int J Mol Sci 2022; 23:ijms23042394. [PMID: 35216509 PMCID: PMC8878297 DOI: 10.3390/ijms23042394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/16/2022] [Accepted: 02/18/2022] [Indexed: 11/16/2022] Open
Abstract
The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features of obesity-associated white adipose tissue (WAT) dysfunction in 66 women with severe obesity without (MetS-) or with MetS (MetS+). Fat cell area, adipocyte size distribution and histological fibrosis were analysed in visceral (VAT) and abdominal subcutaneous WAT (SAT) in 33 age- and BMI-matched pairs of MetS- and MetS+ subjects. The mRNA expression of 93 genes implicated in obesity-associated WAT dysfunction was analysed by RT-qPCR in both fat depots. MetS+ females showed higher adipocyte hypertrophy in both fat depots and increased fibrosis and expression of macrophage and hypoxia markers in SAT. Transcriptional data suggest increased fatty acid oxidation in SAT and impaired thermogenesis and extracellular matrix remodelling in VAT from MetS+ subjects. A sPLS-DA model, including SAT expression of PPARA and LEPR genes identified MetS with an AUC = 0.87. Despite equal age, BMI and body composition, MetS+ females display morphological and transcriptional differences in both WAT depots, especially in SAT. These factors may contribute to the transition to MetS.
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Affiliation(s)
- Óscar Osorio-Conles
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain;
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain;
- Correspondence: (Ó.O.-C.); (A.d.H.); Tel.: +34-932275707 (ext. 2910) (Ó.O.-C.); +34-932279846 (A.d.H.); Fax: +34932275589 (A.d.H.)
| | - Arturo Vega-Beyhart
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain;
| | - Ainitze Ibarzabal
- Gastrointestinal Surgery Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain; (A.I.); (J.M.B.)
| | - José María Balibrea
- Gastrointestinal Surgery Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain; (A.I.); (J.M.B.)
| | - Josep Vidal
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain;
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain;
- Obesity Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
| | - Ana de Hollanda
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain;
- Obesity Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red Fisiopatologia de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
- Correspondence: (Ó.O.-C.); (A.d.H.); Tel.: +34-932275707 (ext. 2910) (Ó.O.-C.); +34-932279846 (A.d.H.); Fax: +34932275589 (A.d.H.)
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24
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Assumpção JAF, Pasquarelli-do-Nascimento G, Duarte MSV, Bonamino MH, Magalhães KG. The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy. J Biomed Sci 2022; 29:12. [PMID: 35164764 PMCID: PMC8842976 DOI: 10.1186/s12929-022-00796-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 02/07/2022] [Indexed: 12/13/2022] Open
Abstract
Obesity is nowadays considered a pandemic which prevalence's has been steadily increasingly in western countries. It is a dynamic, complex, and multifactorial disease which propitiates the development of several metabolic and cardiovascular diseases, as well as cancer. Excessive adipose tissue has been causally related to cancer progression and is a preventable risk factor for overall and cancer-specific survival, associated with poor prognosis in cancer patients. The onset of obesity features a state of chronic low-grade inflammation and secretion of a diversity of adipocyte-derived molecules (adipokines, cytokines, hormones), responsible for altering the metabolic, inflammatory, and immune landscape. The crosstalk between adipocytes and tumor cells fuels the tumor microenvironment with pro-inflammatory factors, promoting tissue injury, mutagenesis, invasion, and metastasis. Although classically established as a risk factor for cancer and treatment toxicity, recent evidence suggests mild obesity is related to better outcomes, with obese cancer patients showing better responses to treatment when compared to lean cancer patients. This phenomenon is termed obesity paradox and has been reported in different types and stages of cancer. The mechanisms underlying this paradoxical relationship between obesity and cancer are still not fully described but point to systemic alterations in metabolic fitness and modulation of the tumor microenvironment by obesity-associated molecules. Obesity impacts the response to cancer treatments, such as chemotherapy and immunotherapy, and has been reported as having a positive association with immune checkpoint therapy. In this review, we discuss obesity's association to inflammation and cancer, also highlighting potential physiological and biological mechanisms underlying this association, hoping to clarify the existence and impact of obesity paradox in cancer development and treatment.
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Affiliation(s)
| | | | - Mariana Saldanha Viegas Duarte
- Immunology and Tumor Biology Program - Research Coordination, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil
| | - Martín Hernan Bonamino
- Immunology and Tumor Biology Program - Research Coordination, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil
- Vice - Presidency of Research and Biological Collections (VPPCB), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Kelly Grace Magalhães
- Laboratory of Immunology and Inflammation, Department of Cell Biology, University of Brasilia, Brasília, DF, Brazil.
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25
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Qian G, Adeyanju O, Sunil C, Huang SK, Chen SY, Tucker TA, Idell S, Guo X. Dedicator of Cytokinesis 2 (DOCK2) Deficiency Attenuates Lung Injury Associated with Chronic High-Fat and High-Fructose Diet-Induced Obesity. THE AMERICAN JOURNAL OF PATHOLOGY 2022; 192:226-238. [PMID: 34767813 PMCID: PMC8883439 DOI: 10.1016/j.ajpath.2021.10.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 09/21/2021] [Accepted: 10/19/2021] [Indexed: 02/06/2023]
Abstract
Obesity is a major risk factor for lung disease development. However, little is known about the impact of chronic high-fat and high-fructose (HFHF) diet-induced obesity on lung inflammation and subsequent pulmonary fibrosis. Herein we hypothesized that dedicator of cytokinesis 2 (DOCK2) promotes a proinflammatory phenotype of lung fibroblasts (LFs) to elicit lung injury and fibrosis in chronic HFHF diet-induced obesity. An HFHF diet for 20 weeks induced lung inflammation and profibrotic changes in wild-type C57BL/6 mice. CD68 and monocyte chemoattractant protein-1 (MCP-1) expression were notably increased in the lungs of wild-type mice fed an HFHF diet. An HFHF diet further increased lung DOCK2 expression that co-localized with fibroblast-specific protein 1, suggesting a role of DOCK2 in regulating proinflammatory phenotype of LFs. Importantly, DOCK2 knockout protected mice from lung inflammation and fibrosis induced by a HFHF diet. In primary human LFs, tumor necrosis factor-α (TNF-α) and IL-1β induced DOCK2 expression concurrent with MCP-1, IL-6, and matrix metallopeptidase 2. DOCK2 knockdown suppressed TNF-α-induced expression of these molecules and activation of phosphatidylinositol 3-kinase/AKT and NF-κB signaling pathways, suggesting a mechanism of DOCK2-mediated proinflammatory and profibrotic changes in human LFs. Taken together, these findings reveal a previously unrecognized role of DOCK2 in regulating proinflammatory phenotype of LFs, potentiation of lung inflammation, and pulmonary fibrosis in chronic HFHF diet-caused obesity.
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Affiliation(s)
- Guoqing Qian
- Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas
| | - Oluwaseun Adeyanju
- Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas
| | - Christudas Sunil
- Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas
| | - Steven K. Huang
- Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan
| | - Shi-You Chen
- Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia,Department of Surgery, School of Medicine, The University of Missouri, Columbia, Missouri
| | - Torry A. Tucker
- Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas
| | - Steven Idell
- Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas
| | - Xia Guo
- Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas,Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia,Address correspondence to Xia Guo, Ph.D., Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Lab A-1, Tyler, TX 75708.
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26
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ArefNezhad R, Motedayyen H, Roghani-Shahraki H. Do cytokines associate periodontitis with metabolic disorders? An overview of current documents. Endocr Metab Immune Disord Drug Targets 2022; 22:778-786. [PMID: 35043774 DOI: 10.2174/1871530322666220119112026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 10/28/2021] [Accepted: 11/26/2021] [Indexed: 11/22/2022]
Abstract
Periodontitis is an oral chronic inflammatory condition affecting the adult population worldwide. Many microorganisms act as an initiator for induction of inflammatory immune responses, which participate in the destruction of connective tissue surrounding the teeth and thereby result in tooth loss. Cytokines may have indispensable roles in its pathogenesis through enhancing inflammatory and immune responses. Cytokines can affect functions of some cells of different tissues, such as the cells of the pancreas, liver, and adipose tissues. There is evidence that periodontitis is associated with metabolic disorders, like liver cirrhosis, obesity, and diabetes mellitus. Hence, this review was focused on determining how cytokines can participate in the correlation of periodontitis with metabolic disorders.
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Affiliation(s)
- Reza ArefNezhad
- Halal Research Center of IRI, FDA, Tehran, Iran
- Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Motedayyen
- Autoimmune Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
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27
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Impact of Bariatric Surgery on Adipose Tissue Biology. J Clin Med 2021; 10:jcm10235516. [PMID: 34884217 PMCID: PMC8658722 DOI: 10.3390/jcm10235516] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/20/2021] [Accepted: 11/22/2021] [Indexed: 02/07/2023] Open
Abstract
Bariatric surgery (BS) procedures are actually the most effective intervention to help subjects with severe obesity achieve significant and sustained weight loss. White adipose tissue (WAT) is increasingly recognized as the largest endocrine organ. Unhealthy WAT expansion through adipocyte hypertrophy has pleiotropic effects on adipocyte function and promotes obesity-associated metabolic complications. WAT dysfunction in obesity encompasses an altered adipokine secretome, unresolved inflammation, dysregulated autophagy, inappropriate extracellular matrix remodeling and insufficient angiogenic potential. In the last 10 years, accumulating evidence suggests that BS can improve the WAT function beyond reducing the fat depot sizes. The causal relationships between improved WAT function and the health benefits of BS merits further investigation. This review summarizes the current knowledge on the short-, medium- and long-term outcomes of BS on the WAT composition and function.
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28
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Song M, Zhang S, Tao Z, Li J, Shi Y, Xiong Y, Zhang W, Liu C, Chen S. MMP-12 siRNA improves the homeostasis of the small intestine and metabolic dysfunction in high-fat diet feeding-induced obese mice. Biomaterials 2021; 278:121183. [PMID: 34653936 DOI: 10.1016/j.biomaterials.2021.121183] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 10/01/2021] [Accepted: 10/07/2021] [Indexed: 12/12/2022]
Abstract
The changes of small intestinal homeostasis have been recognized to contribute essentially to the obese development. However, the core small intestinal regulator which mediates over-nutrient impacts on the homeostasis of the small intestines remains elusive. Here, we identify the MMP-12 as such a responsive factor in mouse small intestines. Taking advantages of the nano delivery system, we demonstrate that small intestine-specific MMP-12 knockdown alleviates high-fat diet feeding-induced metabolic disorders and improves intestinal homeostasis in mice, including a significant decrease in lipid transportation, bile acid reabsorption, and inflammation. In parallel, the small intestinal integrity is recovered and the gut microbiota composition is reversed towards that under normal diet feeding. Mechanistically, MMP-12, differing from its traditional elastolytic function, acts as a transcriptional factor to activate Fabp4 transcription through epigenetic modification. In translational medicine, clinical applications of our nanosystem and therapeutic interventions targeting MMP-12 will benefit patients with obesity and associated diseases.
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Affiliation(s)
- Mingming Song
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Shiyao Zhang
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Zixuan Tao
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Jianning Li
- Nanjing Qixia Hospital, Nanjing, 210046, PR China
| | - Yujie Shi
- Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, PR China
| | - Yonghong Xiong
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Wenxiang Zhang
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Chang Liu
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Siyu Chen
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China.
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29
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Braveman P, Dominguez TP, Burke W, Dolan SM, Stevenson DK, Jackson FM, Collins JW, Driscoll DA, Haley T, Acker J, Shaw GM, McCabe ERB, Hay WW, Thornburg K, Acevedo-Garcia D, Cordero JF, Wise PH, Legaz G, Rashied-Henry K, Frost J, Verbiest S, Waddell L. Explaining the Black-White Disparity in Preterm Birth: A Consensus Statement From a Multi-Disciplinary Scientific Work Group Convened by the March of Dimes. FRONTIERS IN REPRODUCTIVE HEALTH 2021; 3:684207. [PMID: 36303973 PMCID: PMC9580804 DOI: 10.3389/frph.2021.684207] [Citation(s) in RCA: 116] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 07/06/2021] [Indexed: 11/30/2022] Open
Abstract
In 2017-2019, the March of Dimes convened a workgroup with biomedical, clinical, and epidemiologic expertise to review knowledge of the causes of the persistent Black-White disparity in preterm birth (PTB). Multiple databases were searched to identify hypothesized causes examined in peer-reviewed literature, 33 hypothesized causes were reviewed for whether they plausibly affect PTB and either occur more/less frequently and/or have a larger/smaller effect size among Black women vs. White women. While definitive proof is lacking for most potential causes, most are biologically plausible. No single downstream or midstream factor explains the disparity or its social patterning, however, many likely play limited roles, e.g., while genetic factors likely contribute to PTB, they explain at most a small fraction of the disparity. Research links most hypothesized midstream causes, including socioeconomic factors and stress, with the disparity through their influence on the hypothesized downstream factors. Socioeconomic factors alone cannot explain the disparity's social patterning. Chronic stress could affect PTB through neuroendocrine and immune mechanisms leading to inflammation and immune dysfunction, stress could alter a woman's microbiota, immune response to infection, chronic disease risks, and behaviors, and trigger epigenetic changes influencing PTB risk. As an upstream factor, racism in multiple forms has repeatedly been linked with the plausible midstream/downstream factors, including socioeconomic disadvantage, stress, and toxic exposures. Racism is the only factor identified that directly or indirectly could explain the racial disparities in the plausible midstream/downstream causes and the observed social patterning. Historical and contemporary systemic racism can explain the racial disparities in socioeconomic opportunities that differentially expose African Americans to lifelong financial stress and associated health-harming conditions. Segregation places Black women in stressful surroundings and exposes them to environmental hazards. Race-based discriminatory treatment is a pervasive stressor for Black women of all socioeconomic levels, considering both incidents and the constant vigilance needed to prepare oneself for potential incidents. Racism is a highly plausible, major upstream contributor to the Black-White disparity in PTB through multiple pathways and biological mechanisms. While much is unknown, existing knowledge and core values (equity, justice) support addressing racism in efforts to eliminate the racial disparity in PTB.
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Affiliation(s)
- Paula Braveman
- School of Medicine, University of California, San Francisco, San Francisco, CA, United States
| | - Tyan Parker Dominguez
- USC Suzanne Dworak-Peck School of Social Work, University of Southern California, Los Angeles, CA, United States
| | - Wylie Burke
- University of Washington School of Medicine, Seattle, WA, United States
| | - Siobhan M. Dolan
- Albert Einstein College of Medicine, New York, NY, United States
| | | | | | - James W. Collins
- Northwestern University School of Medicine, Chicago, IL, United States
| | - Deborah A. Driscoll
- University of Pennsylvania School of Medicine, Philadelphia, PA, United States
| | - Terinney Haley
- School of Medicine, University of California, San Francisco, San Francisco, CA, United States
| | - Julia Acker
- School of Medicine, University of California, San Francisco, San Francisco, CA, United States
| | - Gary M. Shaw
- Stanford University School of Medicine, Stanford, CA, United States
| | - Edward R. B. McCabe
- David Geffen School of Medicine at University of California, Los Angeles, CA, United States
| | | | - Kent Thornburg
- School of Medicine, Oregon State University, Portland, OR, United States
| | | | - José F. Cordero
- University of Georgia College of Public Health, Athens, GA, United States
| | - Paul H. Wise
- Stanford University School of Medicine, Stanford, CA, United States
| | - Gina Legaz
- March of Dimes, White Plains, NY, United States
| | | | | | - Sarah Verbiest
- University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
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30
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Zipris D. Visceral Adipose Tissue: A New Target Organ in Virus-Induced Type 1 Diabetes. Front Immunol 2021; 12:702506. [PMID: 34421908 PMCID: PMC8371384 DOI: 10.3389/fimmu.2021.702506] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 07/19/2021] [Indexed: 12/14/2022] Open
Abstract
Type 1 diabetes (T1D) is a proinflammatory pathology that leads to the specific destruction of insulin producing β-cells and hyperglycaemia. Much of the knowledge about type 1 diabetes (T1D) has focused on mechanisms of disease progression such as adaptive immune cells and the cytokines that control their function, whereas mechanisms linked with the initiation of the disease remain unknown. It has been hypothesized that in addition to genetics, environmental factors play a pivotal role in triggering β-cell autoimmunity. The BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rats have been used to decipher the mechanisms that lead to virus-induced T1D. Both animals develop β-cell inflammation and hyperglycemia upon infection with the parvovirus Kilham Rat Virus (KRV). Our earlier in vitro and in vivo studies indicated that KRV-induced innate immune upregulation early in the disease course plays a causal role in triggering β-cell inflammation and destruction. Furthermore, we recently found for the first time that infection with KRV induces inflammation in visceral adipose tissue (VAT) detectable as early as day 1 post-infection prior to insulitis and hyperglycemia. The proinflammatory response in VAT is associated with macrophage recruitment, proinflammatory cytokine and chemokine upregulation, endoplasmic reticulum (ER) and oxidative stress responses, apoptosis, and downregulation of adipokines and molecules that mediate insulin signaling. Downregulation of inflammation suppresses VAT inflammation and T1D development. These observations are strikingly reminiscent of data from obesity and type 2 diabetes (T2D) in which VAT inflammation is believed to play a causal role in disease mechanisms. We propose that VAT inflammation and dysfunction may be linked with the mechanism of T1D progression.
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Affiliation(s)
- Danny Zipris
- Innate Biotechnologies LLC, Denver, CO, United States
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Tang C, Kong L, Shan M, Lu Z, Lu Y. Protective and ameliorating effects of probiotics against diet-induced obesity: A review. Food Res Int 2021; 147:110490. [PMID: 34399486 DOI: 10.1016/j.foodres.2021.110490] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 05/05/2021] [Accepted: 05/23/2021] [Indexed: 02/07/2023]
Abstract
Diet-induced obesity is one of the major public health concerns all over the world, and obesity also contributes to the development of other chronic diseases such as non-alcoholic fatty acid liver disease, type 2 diabetes mellitus and cardiovascular diseases. Evidence shows that the pathogenesis of obesity and obesity-associated chronic diseases are closely related to dysregulation of lipid metabolism, glucose metabolism and cholesterol metabolism, and oxidative stress, endoplasmic reticulum stress, abnormal gut microbiome and chronic low-grade inflammation. Recently, in view of potential effects on lipid metabolism, glucose metabolism, cholesterol metabolism and intestinal microbiome, as well as anti-oxidative and anti-inflammatory activities, natural probiotics, including live and dead probiotics, and probiotic components and metabolites, have attracted increasing attention and are considered as novel strategies for preventing and ameliorating obesity and obesity-related chronic diseases. Specifically, this review is presented on the anti-obesity effects of probiotics and underlying molecular mechanisms, which will provide a theoretical basis of anti-obesity probiotics for the development of functional foods.
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Affiliation(s)
- Chao Tang
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Liangyu Kong
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Mengyuan Shan
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Zhaoxin Lu
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China.
| | - Yingjian Lu
- College of Food Science & Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China.
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Abstract
Obesity is epidemiologically linked to 13 forms of cancer. The local and systemic obese environment is complex and likely affect tumors through multiple avenues. This includes modulation of cancer cell phenotypes and the composition of the tumor microenvironment. A molecular understanding of how obesity links to cancer holds promise for identifying candidate genes for targeted therapy for obese cancer patient. Herein, we review both the cell-autonomous and non-cell-autonomous mechanisms linking obesity and cancer as well as provide an overview of the mouse model systems applied to study this.
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Affiliation(s)
- Xiao-Zheng Liu
- Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway
| | - Line Pedersen
- Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway
| | - Nils Halberg
- Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway
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Abstract
Bariatric and metabolic surgery has evolved from simple experimental procedures for a chronic problem associated with significant morbidity into a sophisticated multidisciplinary treatment modality rooted in biology and physiology. Although the complete mechanistic narrative of bariatric surgery cannot yet be written, significant advance in knowledge has been made in the past 2 decades. This article provides a brief overview of the most studied hypotheses and their supporting evidence. Ongoing research, especially in frontier areas, such as the microbiome, will continue to refine, and perhaps even revise, current mechanistic understanding.
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Bifidobacterium adolescentis Isolated from Different Hosts Modifies the Intestinal Microbiota and Displays Differential Metabolic and Immunomodulatory Properties in Mice Fed a High-Fat Diet. Nutrients 2021; 13:nu13031017. [PMID: 33801119 PMCID: PMC8004121 DOI: 10.3390/nu13031017] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 03/15/2021] [Accepted: 03/18/2021] [Indexed: 01/07/2023] Open
Abstract
The incidence of obesity, which is closely associated with the gut microbiota and chronic inflammation, has rapidly increased in the past 40 years. Therefore, the probiotic-based modification of the intestinal microbiota composition has been developed as a strategy for the treatment of obesity. In this study, we selected four Bifidobacterium adolescentis strains isolated from the feces of newborn and elderly humans to investigate whether supplementation with B. adolescentis of various origins could alleviate obesity in mice. Male C57BL/6J mice fed a high-fat diet (HFD, 60% energy as fat) received one of the following 14-week interventions: (i) B. adolescentis N4_N3, (ii) B. adolescentis Z25, (iii) B. adolescentis 17_3, (iv) B. adolescentis 2016_7_2, and (v) phosphate-buffered saline. The metabolic parameters, thermogenesis, and immunity of all treated mice were measured. Cecal and colonic microbial profiles were determined by 16S rRNA gene sequencing. Intestinal concentrations of short-chain fatty acids (SCFAs) were measured by gas chromatography-mass spectrometry (GC-MS). The B. adolescentis strains isolated from the feces of elderly humans (B. adolescentis Z25, 17_3, and 2016_7_2) decreased the body weight or weight gain of mice, whilst the strain isolated from the newborn (B. adolescentis N4_N3) increased the body weight of mice. The B. adolescentis strains isolated from the elderly also increased serum leptin concentrations and induced the expression of thermogenesis- and lipid metabolism-related genes in brown adipose tissue. All the B. adolescentis strains alleviated inflammations in the spleen and brain and modified the cecal and colonic microbiota. Particularly, all strains reversed the HFD-induced depletion of Bifidobacterium and reduced the development of beta-lactam resistance. In addition, the B. adolescentis strains isolated from the elderly increased the relative abundances of potentially beneficial genera, such as Bacteroides, Parabacteroides, and Faecalibaculum. We speculate that such increased abundance of commensal bacteria may have mediated the alleviation of obesity, as B. adolescentis supplementation decreased the intestinal production of SCFAs, thereby reducing energy delivery to the host mice. Our results revealed that certain strains of B. adolescentis can alleviate obesity and modify the gut microbiota of mice. The tested strains of B. adolescentis showed different effects on lipid metabolism and immunity regulation, with these effects related to whether they had been isolated from the feces of newborn or elderly humans. This indicates that B. adolescentis from different sources may have disparate effects on host health possibly due to the transmission of origin-specific functions to the host.
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Pak HJ, Choi HN, Lee HC, Yim JE. Effects of intragastric balloon on obesity in obese Korean women for 6 months post removal. Nutr Res Pract 2021; 15:456-467. [PMID: 34349879 PMCID: PMC8313389 DOI: 10.4162/nrp.2021.15.4.456] [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: 09/10/2020] [Revised: 12/15/2020] [Accepted: 01/07/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND/OBJECTIVES The prevalence of morbid obesity in Korean women has consistently been increasing, while the overall prevalence rate of obesity in Korean women seems to be stable. In addition to bariatric surgery, intragastric balloons (IGBs), as a nonsurgical therapy, have been reported to be effective in weight loss. However, the beneficial effects of IGB in Korean women with obesity have not been fully investigated. The aim of this study was to evaluate the changes in fat mass in Korean women with obesity who had undergone IGB treatment for 6 mon. SUBJECTS/METHODS Seventy-four women with obesity (body mass index [BMI] ≥ 25.0 kg/m2) were recruited. Clinical data, including general information, comorbidities with obesity, anthropometric data, and changes in the body fat composition before and after IGB treatment, were obtained from the subjects. RESULTS Most subjects had one or more comorbidities, such as osteoarthropathy and woman's disease, and had poor eating behaviors, including irregular mealtimes, eating quickly, and frequent overeating. Body composition measurements showed that weight, fat mass, and waist-hip circumference ratio decreased significantly at 6 mon after IGB treatment. In particular, women with morbid obesity (BMI ≥ 30 kg/m2) showed 33% excess weight loss. There was no significant difference in skeletal muscle mass and mineral contents after IGB treatment. CONCLUSIONS This study suggested that 6 mon of IGB treatment can be a beneficial treatment for obesity without muscle mass and bone mineral loss.
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Affiliation(s)
- Hyeon-Ju Pak
- Department of Food and Nutrition, Changwon National University, Changwon 51140, Korea
| | - Ha-Neul Choi
- Department of Food and Nutrition, Changwon National University, Changwon 51140, Korea
| | | | - Jung-Eun Yim
- Department of Food and Nutrition, Changwon National University, Changwon 51140, Korea.,Interdisciplinary Program in Senior Human Ecology (BK21 Four Program), Changwon National University, Changwon 51140, Korea
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Stein RA, Young LM. From ACE2 to COVID-19: A multiorgan endothelial disease. Int J Infect Dis 2020; 100:425-430. [PMID: 32896660 PMCID: PMC7832810 DOI: 10.1016/j.ijid.2020.08.083] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Affiliation(s)
- Richard A Stein
- NYU Tandon School of Engineering, Department of Chemical and Biomolecular Engineering, 6 MetroTech Center, Brooklyn, NY 11201, USA; LaGuardia Community College, Department of Natural Sciences, City University of New York, New York, NY 11101, USA.
| | - Lauren M Young
- University of Chicago, Department of Internal Medicine, 5841 S Maryland Ave, Chicago, IL 60637, USA.
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Abstract
BACKGROUND Due to the rapidly escalating number of cases and the low baseline of overall health in Louisiana, we sought to determine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in hospitalized COVID patients in two major metropolitan areas with the highest prevalence of cases and exceedingly high rates of obesity and other comorbid conditions. We hypothesized that elevated NLR would be a prognostic indicator of mortality. METHODS This was a review of a prospective registry of adult (18+ years) hospitalized Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) patients from two large urban safety net hospitals in Louisiana. Blood cell counts at days 2 and 5 were used to obtain NLR. Receiver operating characteristic curve analysis assessed predictive capacity of NLR on mortality. Kaplan-Meier survival analysis and Cox regression models examined the effect of NLR on survival. RESULTS The study population of 125 patients was majority African American (88.6%) and female (54.8%) with a mean age and body mass index of 58.7 years and 34.2. Most (96.0%) had comorbidities of which hypertension (72.0%), obesity (66.7%), and diabetes (40.0%) were the most common. Mortality was 18.4%. NLR > 4.94 on day 1 predicted intubation (P = 0.02). NLR above established cutoff values on hospital days 2 and 5 each significantly predicted mortality (P < 0.001 and P = 0.002, respectively). CONCLUSIONS NLR is a prognostic factor for endotracheal intubation upon hospital admission and independent predictor for risk of mortality in SARS-CoV-2 patients on subsequent hospital days. Clinical research efforts should examine effects of strategies such as arginase inhibition alone and/or inhaled nitric oxide to ameliorate the effects of elevated NLR.
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Mullins CA, Gannaban RB, Khan MS, Shah H, Siddik MAB, Hegde VK, Reddy PH, Shin AC. Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain. Antioxidants (Basel) 2020; 9:antiox9101018. [PMID: 33092099 PMCID: PMC7589608 DOI: 10.3390/antiox9101018] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 10/15/2020] [Accepted: 10/16/2020] [Indexed: 02/06/2023] Open
Abstract
Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.
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Affiliation(s)
- Caitlyn A. Mullins
- Neurobiology of Nutrition Laboratory, Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; (C.A.M.); (R.B.G.); (H.S.)
| | - Ritchel B. Gannaban
- Neurobiology of Nutrition Laboratory, Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; (C.A.M.); (R.B.G.); (H.S.)
| | - Md Shahjalal Khan
- Obesity and Metabolic Health Laboratory, Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; (M.S.K.); (M.A.B.S.); (V.K.H.)
| | - Harsh Shah
- Neurobiology of Nutrition Laboratory, Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; (C.A.M.); (R.B.G.); (H.S.)
| | - Md Abu B. Siddik
- Obesity and Metabolic Health Laboratory, Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; (M.S.K.); (M.A.B.S.); (V.K.H.)
| | - Vijay K. Hegde
- Obesity and Metabolic Health Laboratory, Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; (M.S.K.); (M.A.B.S.); (V.K.H.)
| | - P. Hemachandra Reddy
- Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79409, USA;
| | - Andrew C. Shin
- Neurobiology of Nutrition Laboratory, Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; (C.A.M.); (R.B.G.); (H.S.)
- Correspondence: ; Tel.: +1-806-834-1713
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Ryan PM, Caplice NM. Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation, and Cytokine Amplification in Coronavirus Disease 2019? Obesity (Silver Spring) 2020; 28:1191-1194. [PMID: 32314868 PMCID: PMC7264526 DOI: 10.1002/oby.22843] [Citation(s) in RCA: 227] [Impact Index Per Article: 45.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 04/15/2020] [Accepted: 04/15/2020] [Indexed: 01/08/2023]
Abstract
Coronavirus disease 2019 (COVID-19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcomes include advanced age, male sex, preexisting cardiovascular disease, and risk factors including hypertension, diabetes, and, more recently, obesity. This article posits new obesity-driven predictors of poor COVID-19 outcomes, over and above the more obvious extant risks associated with obesity, including cardiometabolic disease and hypoventilation syndrome in intensive care patients. This article also outlines a theoretical mechanistic framework whereby adipose tissue in individuals with obesity may act as a reservoir for more extensive viral spread, with increased shedding, immune activation, and cytokine amplification. This paper proposes studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in individuals with obesity and COVID-19. Finally, this paper underscores emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal.
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Affiliation(s)
- Paul MacDaragh Ryan
- Centre for Research in Vascular BiologyAPC Microbiome IrelandUniversity College CorkCork University HospitalCorkIreland
| | - Noel M. Caplice
- Centre for Research in Vascular BiologyAPC Microbiome IrelandUniversity College CorkCork University HospitalCorkIreland
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40
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Gray A, Dang BN, Moore TB, Clemens R, Pressman P. A review of nutrition and dietary interventions in oncology. SAGE Open Med 2020; 8:2050312120926877. [PMID: 32537159 PMCID: PMC7268120 DOI: 10.1177/2050312120926877] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 04/22/2020] [Indexed: 12/11/2022] Open
Abstract
The complex cellular mechanisms and inter-related pathways of cancer proliferation, evasion, and metastasis remain an emerging field of research. Over the last several decades, nutritional research has prominent role in identifying emerging adjuvant therapies in our fight against cancer. Nutritional and dietary interventions are being explored to improve the morbidity and mortality for cancer patients worldwide. In this review, we examine several dietary interventions and their proposed mechanisms against cancer as well as identifying limitations in the currently available literature. This review provides a comprehensive review of the cancer metabolism, dietary interventions used during cancer treatment, anti metabolic drugs, and their impact on nutritional deficiencies along with a critical review of the following diets: caloric restriction, intermittent fasting, ketogenic diet, Mediterranean diet, Japanese diet, and vegan diet.
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Affiliation(s)
- Ashley Gray
- Division of Pediatric Hematology/Oncology, Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Brian N Dang
- David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Theodore B Moore
- Division of Pediatric Hematology/Oncology, Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Roger Clemens
- Pharmacology & Pharmaceutical Sciences, USC School of Pharmacy, International Center for Regulatory Science, Los Angeles, CA, USA
| | - Peter Pressman
- Polyscience Consulting & Director of Nutrition and Public Health, The Daedalus Foundation, San Clemente, CA, USA
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Frommer KW, Hasseli R, Schäffler A, Lange U, Rehart S, Steinmeyer J, Rickert M, Sarter K, Zaiss MM, Culmsee C, Ganjam G, Michels S, Müller-Ladner U, Neumann E. Free Fatty Acids in Bone Pathophysiology of Rheumatic Diseases. Front Immunol 2019; 10:2757. [PMID: 31849953 PMCID: PMC6901602 DOI: 10.3389/fimmu.2019.02757] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 11/11/2019] [Indexed: 01/10/2023] Open
Abstract
Obesity-in which free fatty acid (FFA) levels are chronically elevated-is a known risk factor for different rheumatic diseases, and obese patients are more likely to develop osteoarthritis (OA) also in non-weight-bearing joints. These findings suggest that FFA may also play a role in inflammation-related joint damage and bone loss in rheumatoid arthritis (RA) and OA. Therefore, the objective of this study was to analyze if and how FFA influence cells of bone metabolism in rheumatic diseases. When stimulated with FFA, osteoblasts from RA and OA patients secreted higher amounts of the proinflammatory cytokine interleukin (IL)-6 and the chemokines IL-8, growth-related oncogene α, and monocyte chemotactic protein 1. Receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin, and osteoblast differentiation markers were not influenced by FFA. Mineralization activity of osteoblasts correlated inversely with the level of FFA-induced IL-6 secretion. Expression of the Wnt signaling molecules, axin-2 and β-catenin, was not changed by palmitic acid (PA) or linoleic acid (LA), suggesting no involvement of the Wnt signaling pathway in FFA signaling for osteoblasts. On the other hand, Toll-like receptor 4 blockade significantly reduced PA-induced IL-8 secretion by osteoblasts, while blocking Toll-like receptor 2 had no effect. In osteoclasts, IL-8 secretion was enhanced by PA and LA particularly at the earliest time point of differentiation. Differences were observed between the responses of RA and OA osteoclasts. FFA might therefore represent a new molecular factor by which adipose tissue contributes to subchondral bone damage in RA and OA. In this context, their mechanisms of action appear to be dependent on inflammation and innate immune system rather than Wnt-RANKL pathways.
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Affiliation(s)
- Klaus W. Frommer
- Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Gießen, Giessen, Germany
| | - Rebecca Hasseli
- Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Gießen, Giessen, Germany
| | - Andreas Schäffler
- Department of Internal Medicine III, Endocrinology, Diabetes, Metabolism, Justus-Liebig-University of Giessen, Giessen, Germany
| | - Uwe Lange
- Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Gießen, Giessen, Germany
| | - Stefan Rehart
- Department of Orthopedics and Trauma Surgery, Agaplesion Markus Hospital, Frankfurt, Germany
| | - Jürgen Steinmeyer
- Department of Orthopaedics and Orthopaedic Surgery, University Hospital Giessen and Marburg, Giessen, Germany
| | - Markus Rickert
- Department of Orthopaedics and Orthopaedic Surgery, University Hospital Giessen and Marburg, Giessen, Germany
| | - Kerstin Sarter
- Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Mario M. Zaiss
- Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Carsten Culmsee
- Institute for Pharmacology and Clinical Pharmacy, University of Marburg, Marburg, Germany
- Center for Mind Brain and Behavior (CMBB), Universities of Marburg and Gießen, Marburg, Germany
| | - Goutham Ganjam
- Institute for Pharmacology and Clinical Pharmacy, University of Marburg, Marburg, Germany
- Center for Mind Brain and Behavior (CMBB), Universities of Marburg and Gießen, Marburg, Germany
- Department of Neurology, Philipps University Marburg, Marburg, Germany
| | - Susanne Michels
- Institute for Pharmacology and Clinical Pharmacy, University of Marburg, Marburg, Germany
- Center for Mind Brain and Behavior (CMBB), Universities of Marburg and Gießen, Marburg, Germany
| | - Ulf Müller-Ladner
- Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Gießen, Giessen, Germany
| | - Elena Neumann
- Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Gießen, Giessen, Germany
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Mohan S, R PRM, Brown L, Ayyappan P, G RK. Endoplasmic reticulum stress: A master regulator of metabolic syndrome. Eur J Pharmacol 2019; 860:172553. [PMID: 31325433 DOI: 10.1016/j.ejphar.2019.172553] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 07/04/2019] [Accepted: 07/16/2019] [Indexed: 12/20/2022]
Abstract
Endoplasmic reticulum (ER) stress, a change in the ER homeostasis, leads to initiation of the unfolded protein response (UPR). The primary functions of the UPR are to restore the ER's physiological activity and coordinate the apoptotic and adaptive responses. Pathophysiological conditions that augment ER stress include hypoxia, misfolded and/or mutated protein accumulation, and high glucose. Prolonged ER stress is a critical factor in the pathogenesis of metabolic syndrome including type 2 diabetes mellitus, cardiovascular diseases, atherosclerosis, obesity, and fatty liver disease. UPR is a complex homeostatic pathway between newly synthesized proteins and their maturation, although the regulatory mechanisms contributing to the UPR and the possible therapeutic strategies are yet to be clarified. Therefore, a comprehensive understanding of the underlying molecular mechanisms is necessary to develop therapeutic interventions targeting ER stress response. In this review, we discuss the role of ER stress and UPR signaling in the pathogenesis of metabolic syndrome, highlighting the main functions of UPR components. We have emphasized the use of novel small molecular chemical chaperones, considered as modulators of ER stress. The initial studies with these chemical chaperones are promising, but detailed studies are required to define their efficacy and adverse effects during therapeutic use in humans.
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Affiliation(s)
- Sreelekshmi Mohan
- Biochemistry and Molecular Mechanism Laboratory, Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Industrial Estate, Thiruvananthapuram, 695019, Kerala, India; Academy of Scientific & Innovative Research (AcSIR), New Delhi, India
| | - Preetha Rani M R
- Biochemistry and Molecular Mechanism Laboratory, Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Industrial Estate, Thiruvananthapuram, 695019, Kerala, India; Academy of Scientific & Innovative Research (AcSIR), New Delhi, India
| | - Lindsay Brown
- School of Health and Wellbeing/Functional Foods Research Group, University of Southern Queensland, Toowoomba, QLD, 4350, Australia
| | - Prathapan Ayyappan
- Department of Surgery-Transplant, University of Nebraska Medical Center, Omaha, NE, USA
| | - Raghu K G
- Biochemistry and Molecular Mechanism Laboratory, Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Industrial Estate, Thiruvananthapuram, 695019, Kerala, India; Academy of Scientific & Innovative Research (AcSIR), New Delhi, India.
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Uranga RM, Keller JN. The Complex Interactions Between Obesity, Metabolism and the Brain. Front Neurosci 2019; 13:513. [PMID: 31178685 PMCID: PMC6542999 DOI: 10.3389/fnins.2019.00513] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 05/06/2019] [Indexed: 12/22/2022] Open
Abstract
Obesity is increasing at unprecedented levels globally, and the overall impact of obesity on the various organ systems of the body is only beginning to be fully appreciated. Because of the myriad of direct and indirect effects of obesity causing dysfunction of multiple tissues and organs, it is likely that there will be heterogeneity in the presentation of obesity effects in any given population. Taken together, these realities make it increasingly difficult to understand the complex interplay between obesity effects on different organs, including the brain. The focus of this review is to provide a comprehensive view of metabolic disturbances present in obesity, their direct and indirect effects on the different organ systems of the body, and to discuss the interaction of these effects in the context of brain aging and the development of neurodegenerative diseases.
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Affiliation(s)
- Romina María Uranga
- Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur-Consejo Nacional de Investigaciones Científicas y Técnicas, Bahía Blanca, Argentina
- Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca, Argentina
| | - Jeffrey Neil Keller
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, United States
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Stanisic J, Koricanac G, Kostic M, Stojiljkovic M, Culafic T, Romic S, Tepavcevic S. Low-intensity exercise in the prevention of cardiac insulin resistance-related inflammation and disturbances in NOS and MMP-9 regulation in fructose-fed ovariectomized rats. Appl Physiol Nutr Metab 2019; 44:1219-1229. [PMID: 30897341 DOI: 10.1139/apnm-2018-0785] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Exercise is important nonpharmacological treatment for improvement of insulin sensitivity in menopause. However, its effect on menopausal cardiac insulin resistance is needing further research. We investigated protective effects of low-intensity exercise on cardiac insulin signaling, inflammation, regulation of nitric oxide synthase (NOS) and matrix metalloproteinase 9 (MMP-9) in ovariectomized (OVX) Wistar rats, submitted to 10% fructose solution for 9 weeks. OVX rats were divided into control, sedentary fructose, and exercise fructose groups. Measurements of physical and biochemical characteristics were carried out to evaluate metabolic syndrome development. Messenger RNA and protein levels and phosphorylation of cardiac insulin signaling molecules, endothelial and inducible NOS (eNOS and iNOS), p65 subunit of nuclear factor κB (NFκB), tumor necrosis factor α (TNF-α), suppressor of cytokine signaling 3 (SOCS3), and MMP-9 were analyzed. Fructose increased insulin level, homeostasis model assessment (HOMA) index, and visceral adipose tissue weight, while low-intensity exercise prevented insulin level and HOMA index increase. Fructose also decreased cardiac pAkt (Ser473), peNOS (Ser1177) and increased insulin receptor substrate 1 (IRS1) phosphorylation at Ser307, pNFκB (Ser276) and NFκB and MMP-9 content, without any effect on iNOS, protein-tyrosine phosphatase 1B, TNF-α, and SOCS3. Exercise prevented changes in pIRS1 (Ser307), pAkt (Ser473), peNOS (Ser1177), pNFκB (Ser276), and NFκB expression. In addition, exercise increased pIRS1 (Tyr632), pAkt (Thr308), and eNOS expression. Low-intensity exercise prevented cardiac insulin signaling disarrangement in fructose-fed OVX rats and therefore eNOS dysfunction, as well as pro-inflammatory signaling activation, without effect on tissue remodeling, suggesting physical training as a way to reduce cardiovascular risk.
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Affiliation(s)
- Jelena Stanisic
- Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia.,Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
| | - Goran Koricanac
- Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia.,Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
| | - Milan Kostic
- Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia.,Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
| | - Mojca Stojiljkovic
- Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia.,Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
| | - Tijana Culafic
- Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia.,Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
| | - Snjezana Romic
- Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia.,Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
| | - Snezana Tepavcevic
- Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia.,Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
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Yu T, Zhao L, Zhang JC, Xuan DY. [Impacts of periodontitis on visceral organ weight and weight percentage in obese mice]. HUA XI KOU QIANG YI XUE ZA ZHI = HUAXI KOUQIANG YIXUE ZAZHI = WEST CHINA JOURNAL OF STOMATOLOGY 2018; 36:514-520. [PMID: 30465345 PMCID: PMC7041136 DOI: 10.7518/hxkq.2018.05.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Revised: 07/09/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVE This study aimed to explore the impacts of periodontitis on the visceral weight and weight percentage of obese animal models. METHODS A total of 64 C57BL/6J mice were divided into the following diet groups: high-fat diet (HFD) group (n=36), which was fed with high-fat diet to induce obesity, and low-fat diet (LFD) group (n=28), which was fed with low-fat diet as the control. After 16 weeks on diet, each diet group was divided into periodontitis (P) and control (C) groups. The P groups were induced for periodontitis by ligation with Porphyromonas gingivalis-adhered silk for 5 or 10 days, and the C groups were sham-ligated as the control. Visceral organs were resected and weighed. The organ weight percentage was calculated. RESULTS Compared with the LFD group, the HFD group significantly upregulated the weight and weight percentage of visceral adipose tissue and spleen (P<0.05), upregulated the weight of liver and kidney (P<0.05), and downregulated the weight percentage of liver and kidney (P<0.01). In the HFD group, the weight and weight percentage of spleen were downregulated in the P group (P<0.05), but were upregulated in the 10-day group compared with the 5-day group (P<0.05). CONCLUSIONS Periodontitis can affect the general morphology of the viscera (especially spleen) in obese animal models. Pathological indications in terms of immunometabolism might be present in the correlation between obesity and periodontitis.
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Affiliation(s)
- Ting Yu
- Dept. of Periodontology, Stomatology Hospital of Guangzhou Medical University, Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Guangzhou 510140, China
| | - Li Zhao
- Dept. of Prosthodontics, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China
| | - Jin-Cai Zhang
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing100049, China
| | - Dong-Ying Xuan
- Dept. of Periodontology, Hangzhou Dental Hospital, Savaid Medical School, University of Chinese Academy of Sciences, Hangzhou 310006, China
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Needell JC, Brown MN, Zipris D. Involvement of adipose tissue inflammation and dysfunction in virus-induced type 1 diabetes. J Endocrinol 2018; 238:61-75. [PMID: 29743341 DOI: 10.1530/joe-18-0131] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 05/08/2018] [Indexed: 12/16/2022]
Abstract
The etiopathogenesis of type 1 diabetes (T1D) remains poorly understood. We used the LEW1.WR1 rat model of Kilham rat virus (KRV)-induced T1D to better understand the role of the innate immune system in the mechanism of virus-induced disease. We observed that infection with KRV results in cell influx into visceral adipose tissue soon following infection prior to insulitis and hyperglycemia. In sharp contrast, subcutaneous adipose tissue is free of cellular infiltration, whereas β cell inflammation and diabetes are observed beginning on day 14 post infection. Immunofluorescence studies further demonstrate that KRV triggers CD68+ macrophage recruitment and the expression of KRV transcripts and proinflammatory cytokines and chemokines in visceral adipose tissue. Adipocytes from naive rats cultured in the presence of KRV express virus transcripts and upregulate cytokine and chemokine gene expression. KRV induces apoptosis in visceral adipose tissue in vivo, which is reflected by positive TUNEL staining and the expression of cleaved caspase-3. Moreover, KRV leads to an oxidative stress response and downregulates the expression of adipokines and genes associated with mediating insulin signaling. Activation of innate immunity with Poly I:C in the absence of KRV leads to CD68+ macrophage recruitment to visceral adipose tissue and a decrease in adipokine expression detected 5 days following Poly (I:C) treatment. Finally, proof-of-principle studies show that brief anti-inflammatory steroid therapy suppresses visceral adipose tissue inflammation and protects from virus-induced disease. Our studies provide evidence raising the hypothesis that visceral adipose tissue inflammation and dysfunction may be involved in early mechanisms triggering β cell autoimmunity.
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Affiliation(s)
- James C Needell
- Barbara Davis Center for Childhood DiabetesUniversity of Colorado Denver, Aurora, Colorado, USA
| | - Madalyn N Brown
- Barbara Davis Center for Childhood DiabetesUniversity of Colorado Denver, Aurora, Colorado, USA
| | - Danny Zipris
- Barbara Davis Center for Childhood DiabetesUniversity of Colorado Denver, Aurora, Colorado, USA
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Ray I, Bhattacharya A, De RK. OCDD: an obesity and co-morbid disease database. BioData Min 2017; 10:33. [PMID: 29201145 PMCID: PMC5697160 DOI: 10.1186/s13040-017-0153-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 11/03/2017] [Indexed: 12/30/2022] Open
Abstract
Background Obesity is a medical condition that is known for increased body mass index (BMI). It is also associated with chronic low level inflammation. Obesity disrupts the immune-metabolic homeostasis by changing the secretion of adipocytes. This affects the end-organs, and gives rise to several diseases including type 2 diabetes, asthma, non-alcoholic fatty liver diseases and cancers. These diseases are known as co-morbid diseases. Several studies have explored the underlying molecular mechanisms of developing obesity associated comorbid diseases. To understand the development and progression of diseases associated with obesity, we need a detailed scenario of gene interactions and the distribution of the responsible genes in human system. Results Obesity and Co-morbid Disease Database (OCDD) is designed for relating obesity and its co-morbid diseases using literature mining, and computational and systems biology approaches. OCDD is aimed to investigate the genes associated with comorbidity. Several existing databases have been used to extract molecular interactions and functional annotations of each gene. The degree of co-morbid associations has been measured and made available to the users. The database is available at http://www.isical.ac.in/~systemsbiology/OCDD/home.php Conclusions The main objective of the database is to derive the relations among the genes that are involved in both obesity and its co-morbid diseases. Functional annotation of common genes, gene interaction networks and key driver analyses have made the database a valuable and comprehensive resource for investigating the causal links between obesity and co-morbid diseases. Electronic supplementary material The online version of this article (doi:10.1186/s13040-017-0153-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Indrani Ray
- Machine Intelligence Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata, 700108 India
| | - Anindya Bhattacharya
- Department of Computer Science and Engineering, University of California, 9500 Gilman Drive, La Jolla, San Diego, 92093 CA USA
| | - Rajat K De
- Machine Intelligence Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata, 700108 India
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Tariq M, Zhang J, Liang G, Ding L, He Q, Yang B. Macrophage Polarization: Anti-Cancer Strategies to Target Tumor-Associated Macrophage in Breast Cancer. J Cell Biochem 2017; 118:2484-2501. [DOI: 10.1002/jcb.25895] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 01/18/2017] [Indexed: 12/11/2022]
Affiliation(s)
- Muhammad Tariq
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research; Institute of Pharmacology and Toxicology; College of Pharmaceutical Sciences; Zhejiang University; Hangzhou 310058 China
| | - Jieqiong Zhang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research; Institute of Pharmacology and Toxicology; College of Pharmaceutical Sciences; Zhejiang University; Hangzhou 310058 China
| | - Guikai Liang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research; Institute of Pharmacology and Toxicology; College of Pharmaceutical Sciences; Zhejiang University; Hangzhou 310058 China
| | - Ling Ding
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research; Institute of Pharmacology and Toxicology; College of Pharmaceutical Sciences; Zhejiang University; Hangzhou 310058 China
| | - Qiaojun He
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research; Institute of Pharmacology and Toxicology; College of Pharmaceutical Sciences; Zhejiang University; Hangzhou 310058 China
| | - Bo Yang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research; Institute of Pharmacology and Toxicology; College of Pharmaceutical Sciences; Zhejiang University; Hangzhou 310058 China
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Belemets N, Kobyliak N, Virchenko O, Falalyeyeva T, Olena T, Bodnar P, Savchuk O, Galenova T, Caprnda M, Rodrigo L, Skladany L, Delev D, Opatrilova R, Kruzliak P, Beregova T, Ostapchenko L. Effects of polyphenol compounds melanin on NAFLD/NASH prevention. Biomed Pharmacother 2017; 88:267-276. [DOI: 10.1016/j.biopha.2017.01.028] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 12/25/2016] [Accepted: 01/04/2017] [Indexed: 12/17/2022] Open
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Azeez OI, Myburgh JG, Meintjes RA, Oosthuizen MC, Chamunorwa JP. Histomorphology, ultrastructure and fatty acid composition of the adipose tissue in pansteatitis, the potentials in understanding the underlying mechanism and diagnosis of pansteatitis in the Nile crocodile. Lipids Health Dis 2017; 16:47. [PMID: 28231818 PMCID: PMC5324266 DOI: 10.1186/s12944-016-0405-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 12/29/2016] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND In an effort to characterize the fat body and other adipose tissue in the Nile crocodile and the effects of pansteatitis on the structure and composition of the adipose tissue, we evaluated the regional variation in structure and fatty acid composition of healthy farmed crocodiles and those affected by pansteatitis. METHODS Adipose tissue samples were collected from the subcutaneous, visceral and intramuscular fat and the abdominal fat body of ten 4-year old juvenile crocodiles from Izinthaba Crocodile Farm, Pretoria, South Africa while pansteatitis samples were collected from visceral and intramuscular fat of crocodiles that had died of pansteatitis at the Olifant River, Mpumalanga, also in South Africa. Histomorphology, ultrastrustucture and fatty acid composition by fatty acid methyl ester (FAME) analysis were conducted. RESULTS Histological examination showed regional variations in the adipose tissue especially in the collagen content of the ECM, tissue perfusion and division into lobes and lobules by fibrous capsule. Considerable fibrosis, mononuclear cell infiltration especially by macrophages and lymphocytes and toxic changes in the nucleus were observed in the pansteatitis samples. Regional variation in lipid composition especially in Myristoleic (C14:1), Erucic acid (C22:1n9), and Docosadienoic acid (C22:2n6) was observed. Most of the saturated and trans fatty acids were found in significant quantities in the pansteatitis samples, but had very low levels of the cis fatty acid and the essential fatty acids with C18 backbone. CONCLUSION This study demonstrates that there exists some regional variation in histomorphology and fatty acid composition in the healthy adipose tissue of the Nile crocodile. It also showed that pansteatitis in the Nile crocodile might have been triggered by sudden change in energy balance from consumption of dead fish; and probable exposure to toxic environmental conditions with the evidence of up scaled monounsaturated long chain fatty acids composition and toxic changes in the leucocytes observed in pansteatitis in the present study.
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Affiliation(s)
- O I Azeez
- Anatomy and Physiology Department, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, Pretoria, South Africa. .,Department of Veterinary Physiology, Biochemistry and Pharmacology, University of Ibadan, Ibadan, Nigeria.
| | - J G Myburgh
- Paraclinical Science Department, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, Pretoria, South Africa
| | - R A Meintjes
- Anatomy and Physiology Department, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, Pretoria, South Africa
| | - M C Oosthuizen
- Veterinary Tropical Diseases Department, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, Pretoria, South Africa
| | - J P Chamunorwa
- Anatomy and Physiology Department, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, Pretoria, South Africa
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