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Wei X, Guo Z, Zhang T, Liang J. A New Risk Score Based on Lipid Indicators for Patients with Advanced Hepatocellular Carcinoma. J Hepatocell Carcinoma 2025; 12:107-121. [PMID: 39867263 PMCID: PMC11762032 DOI: 10.2147/jhc.s505028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 01/04/2025] [Indexed: 01/28/2025] Open
Abstract
Background The prognosis is extremely troubling in advanced hepatocellular carcinoma (HCC). Prognostic scores have been developed. Yet, the positive predictive values might appear inadequate. This retrospective study aimed to develop a quick and efficient risk score to assess prognosis and clinical response. Methods A total of 391 hCC patients were enrolled and were divided into training and validation groups between 2015 and 2024. Patients were separated into high-risk and low-risk groups using X-tile software. Using the COX proportional risk model analysis method, we then created a risk score and examined them using Kaplan-Meier, time-dependent receiver operating characteristics (ROC) curve, and nomogram analysis. Results In predicting overall survival (OS), free fatty acid/high-density lipoprotein cholesterol (FFHL), tumor size, and BCLC stage were independent prognostic variables. A new risk score was developed just above and used as a prognostic factor (p < 0.001 in the training and validation groups) and had a high time-dependent ROC for progress-free survival (PFS) (area under the curve [AUC] 0.688-0.789 in the training group; AUC 0.592-0.741 in the validation group) and OS (AUC 0.812-0.918 in the training group; AUC 0.692-0.981 in the validation group). In comparison to the best overall response (BOR), the score offered a more accurate evaluation of durable clinical benefit (DCB) (p < 0.001 in the training and validation group; p = 0.061 vs 0.001 in the training and validation group). Conclusion A new score based on lipid markers is a useful tool for evaluating prognosis and distinguishing patients with DCB.
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Affiliation(s)
- Xing Wei
- Department of Medical Oncology, Peking University International Hospital, Beijing, People’s Republic of China
| | - Ziwei Guo
- Department of Medicine, Double Crane Runchuang Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China
| | - Tingting Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, People’s Republic of China
| | - Jun Liang
- Department of Medical Oncology, Peking University International Hospital, Beijing, People’s Republic of China
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Sulaiman U, Vaughan R, Siegel P, Liu D, Gilbert E, Cline M. Embryonic Thermal Programming and Dietary Baicalein Supplementation Post-Hatch: Effects on Broiler Adipose Tissue Deposition. Animals (Basel) 2024; 14:3563. [PMID: 39765466 PMCID: PMC11672455 DOI: 10.3390/ani14243563] [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: 10/16/2024] [Revised: 11/25/2024] [Accepted: 12/06/2024] [Indexed: 01/11/2025] Open
Abstract
Optimization of growth performance and fat metabolism in broilers are critical for meat quality and overall production efficiency. This experiment investigated the effects of dietary baicalein supplementation and embryonic heat conditioning (EHC) on the growth performance and adipose tissue metabolism of 10-day old broilers. Fertile eggs were divided into control and EHC groups, with EHC eggs exposed to intermittent heating (39.5 °C) from day 7 to day 16 of incubation. Hatched chicks were further divided into four groups: CC (control control), CT (control treatment with baicalein), EC (embryonic heat control), and ET (embryonic heat treatment with baicalein), and were fed ad libitum. On day 10 post-hatch, blood and adipose tissue samples were collected for analysis. C/EBPα mRNA was lower in the ET group compared to the EC group and higher in the CT group compared to the CC group. PPARγ and HSL mRNAs were elevated in both the ET and CT groups relative to their controls. Additionally, plasma non-esterified fatty acid (NEFA) levels were significantly higher in the CT group compared to the CC group. These results indicate that baicalein supplementation, particularly when combined with embryonic heat conditioning, can modulate fat metabolism and potentially improve the growth performance of broilers, thereby offering insights into strategies for enhancing poultry production.
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Affiliation(s)
- Usman Sulaiman
- School of Animal Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA; (U.S.); (P.S.)
| | - Reagan Vaughan
- Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA; (R.V.); (D.L.)
| | - Paul Siegel
- School of Animal Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA; (U.S.); (P.S.)
| | - Dongmin Liu
- Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA; (R.V.); (D.L.)
| | - Elizabeth Gilbert
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA;
| | - Mark Cline
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA;
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Bao Y, Shen Y, Zhao W, Yang B, Zhao X, Tao S, Sun P, Monroig Ó, Zhou Q, Jin M. Evaluation of the Optimum Dietary Arachidonic Acid Level and Its Essentiality for Black Seabream ( Acanthopagrus schlegelii): Based on Growth and Lipid Metabolism. AQUACULTURE NUTRITION 2024; 2024:5589032. [PMID: 39575180 PMCID: PMC11581799 DOI: 10.1155/2024/5589032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 05/11/2024] [Accepted: 10/09/2024] [Indexed: 11/24/2024]
Abstract
The aim of this study was to investigate how dietary arachidonic acid (ARA) level affects growth performance and lipid metabolism in juvenile black seabream (Acanthopagrus schlegelii). A feeding trial was conducted for 8 weeks, during which the fish (0.99 ± 0.10 g) were fed six isonitrogenous and isolipidic diets with varying ARA levels of 0.1%, 0.59%, 1.04%, 1.42%, 1.94%, and 2.42%. Fish fed the diet with 1.42% ARA had significantly higher weight gain (WG) and specific growth rate (SGR) than the other groups (p < 0.05), except for the ARA1.04. As the ARA level increased, the liver and muscle effectively accumulated n-6 polyunsaturated fatty acids (n-6 PUFAs; p < 0.05). However, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and n-3 PUFA contents of liver and muscle significantly decreased by increasing dietary ARA level (p < 0.05). Results of liver histology showed dramatically increased vacuolar fat droplets leading to hepatic fat pathological changes in fish fed diets with ARA levels of 1.94% and 2.42% (p < 0.05). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities increased with increasing dietary ARA level which was accompanied with elevated liver lipid content (p < 0.05). Consistently, triglyceride (TG) and nonesterified fatty acid (NEFA) concentrations of serum and liver, and serum cholesterol (CHO) concentration increased (p < 0.05). As the level of dietary ARA increased, the indicators of lipid metabolism such as sirtuin 1 (sirt1) and peroxisome proliferator-activated receptor α (pparα) also increased (p < 0.05). However, after reaching their peak in ARA1.04 group, the level of these indicators declined (p < 0.05). The same trend was observed for the expression of genes related to the downstream pathways. While the mRNA levels of sterol regulatory element-binding protein-1 (srebp-1) and its downstream genes were markedly increased with the increase of dietary ARA level (p < 0.05). In conclusion, these data suggested that the optimum dietary ARA requirement of A. schlegelii is 1.03% of diet based on the WG. The study revealed that a diet containing 1.04% ARA can activate the expression levels of sirt1 and pparα leading to promoted lipolysis. However, dietary ARA levels of ≥1.42% induced lipid accumulation in the liver, as they suppressed the mRNA levels of sirt1 and pparα, while elevating the expression level of genes related to lipogenesis.
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Affiliation(s)
- Yangguang Bao
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China
- Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China
| | - Yuedong Shen
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China
- Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China
| | - Wenli Zhao
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China
- Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China
| | - Bingqian Yang
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China
- Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China
| | - Xiaoyi Zhao
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China
- Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China
| | - Shunshun Tao
- Xiangshan Harbor Aquatic Seedling Co. Ltd., Xiangshan County Fisheries Bureau, Ningbo 315702, China
| | - Peng Sun
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China
- Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China
| | - Óscar Monroig
- Instituto de Acuicultura Torre de la Sal (IATS), CSIC, Ribera de Cabanes 12595, Castellon, Spain
| | - Qicun Zhou
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China
- Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China
| | - Min Jin
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China
- Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China
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Song S, Qiu R, Huang Y, Zhou Z, Yan J, Ou Q, Wei D, He J, Liang Y, Du X, Yao W, Lu T. Study on the mechanism of hepatotoxicity of Aucklandiae radix through liver metabolomics and network pharmacology. Toxicol Res (Camb) 2024; 13:tfae123. [PMID: 39119266 PMCID: PMC11303830 DOI: 10.1093/toxres/tfae123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 07/15/2024] [Accepted: 08/02/2024] [Indexed: 08/10/2024] Open
Abstract
Background Aucklandiae Radix (CAR) and its roasted processed products (PAR) are extensively used in various Chinese patent medicines due to their diverse pharmacological activities. However, numerous side effects of CAR have been reported and the hepatotoxicity and the corresponding mechanisms have not been thoroughly investigated. Our study aims to explore the underlying mechanism of the hepatotoxic impacts of CAR. Methods In this study, metabolomic analysis was performed using liver tissue from the mice administered with different dosages of CAR/PAR extracts to examine the hepatotoxic impacts of CAR and elucidate the underlying mechanism. Network pharmacology was employed to predict the potential molecular targets and associated signaling pathways based on the distinctive compounds between CAR and PAR. A composition-target-GO-Bio process-metabolic pathway network was constructed by integrating the hepatotoxicity-related metabolic pathways. Finally, the target proteins related with the hepatotoxic effect of CAR were identified and validated in vivo. Results The metabolomics analysis revealed that 33 related metabolic pathways were significantly altered in the high-dose CAR group, four of which were associated with the hepatotoxicity and could be alleviated by PAR. The network identified NQO1 as the primary target of the hepatotoxic effect induced by CAR exposure, which was subsequently verified by Western Blotting. Further evidence in vivo demonstrated that Nrf2 and HO-1, closely related to NQO1, were also the main targets through which CAR induced the liver injury, and that oxidative stress should be the primary mechanism for the CAR-induced hepatotoxicity. Conclusions This preliminary study on the hepatic toxic injury of CAR provides a theoretical basis for the rational and safe use of CAR rationally and safely in clinical settings.
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Affiliation(s)
- Shen Song
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Rongli Qiu
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Yan Huang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Zhuxiu Zhou
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Jin Yan
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Qiaochan Ou
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Donghui Wei
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Jingxuan He
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Yi Liang
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Xingyue Du
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Weifeng Yao
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
| | - Tulin Lu
- School of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Road 138, Nanjing 210023, China
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Gutiérrez-Cuevas J, López-Cifuentes D, Sandoval-Rodriguez A, García-Bañuelos J, Armendariz-Borunda J. Medicinal Plant Extracts against Cardiometabolic Risk Factors Associated with Obesity: Molecular Mechanisms and Therapeutic Targets. Pharmaceuticals (Basel) 2024; 17:967. [PMID: 39065815 PMCID: PMC11280341 DOI: 10.3390/ph17070967] [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: 07/01/2024] [Revised: 07/16/2024] [Accepted: 07/18/2024] [Indexed: 07/28/2024] Open
Abstract
Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to the development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease, hypertension, heart failure, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen and C-reactive protein, and others, all of which increase the risk of CVD events. The mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokine dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left-ventricular remodeling and diastolic dysfunction. Natural products of plants provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discuss the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herb and plant extracts for the prevention and treatment of CRFs are also reviewed.
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Affiliation(s)
- Jorge Gutiérrez-Cuevas
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico; (D.L.-C.); (A.S.-R.); (J.A.-B.)
| | - Daniel López-Cifuentes
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico; (D.L.-C.); (A.S.-R.); (J.A.-B.)
- Doctorate in Sciences in Molecular Biology in Medicine, University Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Ana Sandoval-Rodriguez
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico; (D.L.-C.); (A.S.-R.); (J.A.-B.)
| | - Jesús García-Bañuelos
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico; (D.L.-C.); (A.S.-R.); (J.A.-B.)
| | - Juan Armendariz-Borunda
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University Center of Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico; (D.L.-C.); (A.S.-R.); (J.A.-B.)
- Escuela de Medicina y Ciencias de la Salud (EMCS), Tecnologico de Monterrey, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico
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Aarnio R, Kirjavainen A, Rajander J, Forsback S, Kalliokoski K, Nuutila P, Milicevic Z, Coskun T, Haupt A, Laitinen I, Haaparanta-Solin M. New improved radiometabolite analysis method for [ 18F]FTHA from human plasma: a test-retest study with postprandial and fasting state. EJNMMI Res 2024; 14:53. [PMID: 38869780 DOI: 10.1186/s13550-024-01114-5] [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: 04/25/2024] [Accepted: 05/28/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Fatty acid uptake can be measured using PET and 14-(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA). However, the relatively rapid rate of [18F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [18F]FTHA (parent fraction). Here we present a new radiometabolite analysis (RMA) method, with comparison to a previous method for parent fraction analysis, and its use in a test-retest clinical study under fasting and postprandial conditions. We developed a new thin-layer chromatography (TLC) RMA method for analysis of [18F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [18F]FTHA, its radiometabolites, and plasma radioactivity from subjects participating in a clinical study. A total of 17 obese or overweight participants were dosed with [18F]FTHA twice under fasting, and twice under postprandial conditions and plasma samples were obtained between 14 min (mean of first sample) and 72 min (mean of last sample) post-injection. Aliquots of 70 plasma samples were analyzed using both methods, enabling head-to-head comparisons. We performed test-retest and group comparisons of the parent fraction and plasma radioactivity. RESULTS The new TLC method separated seven [18F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [18F]FTHA. From the plasma samples, the mean parent fraction value was on average 7.2 percentage points lower with the new method, compared to the previous method. Repeated [18F]FTHA investigations on the same subject revealed reproducible plasma SUV and parent fractions, with different kinetics between the fasted and postprandial conditions. CONCLUSIONS The newly developed improved radio-TLC method for [18F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [18F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [18F]FTHA metabolic rate under different study settings. TRIAL REGISTRATION EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic. CLINICALTRIALS gov/ct2/show/NCT05132335 .
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Affiliation(s)
- Richard Aarnio
- MediCity Research Laboratory, University of Turku, Turku, Finland.
- Drug Research Doctoral Programme, University of Turku, Turku, Finland.
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, Turku, FI-20520, Finland.
| | - Anna Kirjavainen
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, Turku, FI-20520, Finland
| | - Johan Rajander
- Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland
| | - Sarita Forsback
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, Turku, FI-20520, Finland
| | - Kari Kalliokoski
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, Turku, FI-20520, Finland
| | - Pirjo Nuutila
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, Turku, FI-20520, Finland
- Department of Endocrinology, Turku University Hospital, Turku, Finland
| | | | | | - Axel Haupt
- Eli Lilly and Company, Indianapolis, IN, USA
| | | | - Merja Haaparanta-Solin
- MediCity Research Laboratory, University of Turku, Turku, Finland
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, Turku, FI-20520, Finland
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Kwak YB, Yoo HH, Yoon J. The impact of the administration of red ginseng ( Panax ginseng) on lipid metabolism and free fatty acid profiles in healthy horses using a molecular networking approach. Front Vet Sci 2024; 11:1285000. [PMID: 38332753 PMCID: PMC10851614 DOI: 10.3389/fvets.2024.1285000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 01/08/2024] [Indexed: 02/10/2024] Open
Abstract
This study investigated the potential benefits of the administration of red ginseng (RG) on lipid metabolism and the profiles of individual free fatty acids (FFAs) in healthy horses. Eight healthy horses, raised under similar conditions, were randomly divided into two groups, each comprising four horses. The experimental group received powdered RG (600 mg/kg/day) mixed with a carrier, and the control group received only the carrier. The parameters associated with lipid metabolism and probable adverse effects were evaluated in both groups after 3 weeks. The computational molecular networking (MN) approach was applied to analyze the FFA profiles. The results indicated that RG administration significantly reduced blood triglyceride levels in the experimental group. Analysis of the FFAs using MN revealed significant decreases in specific types of FFAs (C12:0, dodecanoic acid; C14:0, myristric acid; C18:1, oleic acid; C18:2, linoleic acid). RG consumption did not produce significant adverse effects on the renal, hepatic, and immune functions. Thus, RG was found to effectively modulate lipid metabolism and the levels of individual FFAs. The application of the MN for the analysis of FFAs represents a novel approach and can be considered for future research.
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Affiliation(s)
- Young Beom Kwak
- Racing Laboratory, Korea Racing Authority, Jeju, Republic of Korea
| | - Hye Hyun Yoo
- Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Republic of Korea
| | - Jungho Yoon
- Equine Referral Clinic, Jeju Stud Farm, Korea Racing Authority, Jeju, Republic of Korea
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Goulet N, Tetzlaff EJ, Morin R, Mauger J, Amaratunga R, Kenny GP, Imbeault P. No impact of a high-fat meal coupled with intermittent hypoxemia on acute kidney injury biomarkers in adults with and without obstructive sleep apnea. Physiol Rep 2023; 11:e15804. [PMID: 37653582 PMCID: PMC10471792 DOI: 10.14814/phy2.15804] [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: 05/29/2023] [Revised: 08/04/2023] [Accepted: 08/16/2023] [Indexed: 09/02/2023] Open
Abstract
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxemia, which is associated with progressive loss of kidney function, where postprandial fluctuations in renal physiology may further compromise oxygen supply and kidney function. Therefore, we measured biomarkers of acute kidney injury (AKI) following a high-fat meal with and without intermittent hypoxemia. Eighteen healthy young men (mean age [SD]: 22.7 years [3.1]) and seven middle-aged to older individuals with OSA (54.4 years [6.4]) consumed a high-fat meal during normoxia or intermittent hypoxemia (~15 hypoxic cycles per hour, ~85% oxyhemoglobin saturation) for 6 h. We observed no changes in estimated glomerular filtration rate and plasma concentrations of creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) at any measured time points. In both groups, plasma concentrations of interleukin-18 (IL-18) increased after 6 h during normoxia only (p = 0.033, ηp 2 = 0.122), and plasma concentrations of liver-type fatty acid-binding protein (L-FABP) transiently decreased after 3 h in both conditions (p = 0.008, ηp 2 = 0.152). These findings indicate that AKI biomarkers are not acutely elevated during the postprandial state with or without intermittent hypoxemia, suggesting that other mechanisms may play more important roles in the progression of kidney disease in OSA.
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Affiliation(s)
- Nicholas Goulet
- Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health SciencesUniversity of OttawaOttawaOntarioCanada
- Human and Environmental Physiology Research Unit, School of Human Kinetics, Faculty of Health SciencesUniversity of OttawaOttawaOntarioCanada
| | - Emily J. Tetzlaff
- Human and Environmental Physiology Research Unit, School of Human Kinetics, Faculty of Health SciencesUniversity of OttawaOttawaOntarioCanada
| | - Renée Morin
- Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health SciencesUniversity of OttawaOttawaOntarioCanada
| | - Jean‐François Mauger
- Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health SciencesUniversity of OttawaOttawaOntarioCanada
| | | | - Glen P. Kenny
- Human and Environmental Physiology Research Unit, School of Human Kinetics, Faculty of Health SciencesUniversity of OttawaOttawaOntarioCanada
| | - Pascal Imbeault
- Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health SciencesUniversity of OttawaOttawaOntarioCanada
- Institut du Savoir MontfortMontfort HospitalOttawaOntarioCanada
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Zhang X, Yun Y, Lai Z, Ji S, Yu G, Xie Z, Zhang H, Zhong X, Wang T, Zhang L. Supplemental Clostridium butyricum modulates lipid metabolism by reshaping the gut microbiota composition and bile acid profile in IUGR suckling piglets. J Anim Sci Biotechnol 2023; 14:36. [PMID: 36907895 PMCID: PMC10009951 DOI: 10.1186/s40104-023-00828-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 01/03/2023] [Indexed: 03/14/2023] Open
Abstract
BACKGROUND Intrauterine growth restriction (IUGR) can cause lipid disorders in infants and have long-term adverse effects on their growth and development. Clostridium butyricum (C. butyricum), a kind of emerging probiotics, has been reported to effectively attenuate lipid metabolism dysfunctions. Therefore, the objective of this study was to investigate the effects of C. butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets. METHODS Sixteen IUGR and eight normal birth weight (NBW) neonatal male piglets were used in this study. From d 3 to d 24, in addition to drinking milk, the eight NBW piglets (NBW-CON group, n = 8) and eight IUGR piglets (IUGR-CON group, n = 8) were given 10 mL sterile saline once a day, while the remaining IUGR piglets (IUGR-CB group, n = 8) were orally administered C. butyricum at a dose of 2 × 108 colony-forming units (CFU)/kg body weight (suspended in 10 mL sterile saline) at the same frequency. RESULTS The IUGR-CON piglets exhibited restricted growth, impaired hepatic morphology, disordered lipid metabolism, increased abundance of opportunistic pathogens and altered ileum and liver bile acid (BA) profiles. However, C. butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets, characterized by a decreased abundance of opportunistic pathogens in the ileum, including Streptococcus and Enterococcus. The decrease in these bile salt hydrolase (BSH)-producing microbes increased the content of conjugated BAs, which could be transported to the liver and function as signaling molecules to activate liver X receptor α (LXRα) and farnesoid X receptor (FXR). This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol. As a result, the growth performance and morphological structure of the liver improved in the IUGR piglets. CONCLUSION These results indicate that C. butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes (Streptococcus and Enterococcus). This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRα and FXR. The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.
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Affiliation(s)
- Xin Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Yang Yun
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Zheng Lai
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Shuli Ji
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Ge Yu
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Zechen Xie
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Hao Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Xiang Zhong
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Tian Wang
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China
| | - Lili Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China.
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Role of bile acid receptor FXR in development and function of brown adipose tissue. Biochim Biophys Acta Mol Cell Biol Lipids 2023; 1868:159257. [PMID: 36402299 DOI: 10.1016/j.bbalip.2022.159257] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 10/29/2022] [Accepted: 11/03/2022] [Indexed: 11/18/2022]
Abstract
Bile acids act as signalling molecules that contribute to maintenance of energy homeostasis in mice and humans. Activation of G-protein-coupled bile acid receptor TGR5 induces energy expenditure in brown adipose tissue (BAT). However, a role for the nuclear bile acid receptor Farnesoid X receptor (FXR) in BAT has remained ambiguous. We aimed to study the potential role of FXR in BAT development and functioning. Here we demonstrate low yet detectable expression of the α1/2 isoforms of FXR in murine BAT that markedly decreases upon cold exposure. Moderate adipose tissue-specific FXR overexpression in mice induces pronounced BAT whitening, presenting with large intracellular lipid droplets and extracellular collagen deposition. Expression of thermogenic marker genes including the target of Tgr5, Dio2, was significantly lower in BAT of chow-fed aP2-hFXR mice compared to wild-type controls. Transcriptomic analysis revealed marked up-regulation of extracellular matrix formation and down-regulation of mitochondrial functions in BAT from aP2-hFXR mice. In addition, markers of cell type lineages deriving from the dermomyotome, such as myocytes, as well as markers of cellular senescence were strongly induced. The response to cold and β3-adrenergic receptor agonism was blunted in these mice, yet resolved BAT whitening. Newborn cholestatic Cyp2c70-/- mice with a human-like bile acid profile also showed distinct BAT whitening and upregulation of myocyte-specific genes, while thermogenic markers were down-regulated. Ucp1 expression inversely correlated with plasma bile acid levels. Therefore, bile acid signalling via FXR has a role in BAT function already early in tissue development. Functionally, FXR activation appears to oppose TGR5-mediated thermogenesis.
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Ferreira M, Garzón A, Oliva M, Cian R, Drago S, D'Alessandro M. Lipid-lowering effect of microencapsulated peptides from brewer's spent grain in high-sucrose diet-fed rats. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.101981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Aiassa V, Del Rosario Ferreira M, Villafañe N, Eugenia D'Alessandro M. α-Linolenic acid rich-chia seed modulates visceral adipose tissue collagen deposition, lipolytic enzymes expression, insulin signaling and GLUT-4 levels in a diet-induced adiposity rodent model. Food Res Int 2022; 156:111164. [PMID: 35651030 DOI: 10.1016/j.foodres.2022.111164] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 02/28/2022] [Accepted: 03/15/2022] [Indexed: 11/19/2022]
Abstract
Given obesity and its associated metabolic disorders have reached epidemic proportions, the study of therapeutic strategies targeting white adipose tissue (WAT) are of main research interest. We previously shown that α-linolenic acid-rich chia seed was able to ameliorate a wide range of metabolic disorders including body fat accretion in sucrose-rich diet (SRD)-fed rats, an experimental model of visceral adiposity and insulin resistance. However, the mechanisms involved are not fully clarified. The aim of this study was to evaluate the effect of chia seed administration upon WAT remodeling and key enzymes that controls lipolysis, insulin signaling (tAKT, pAKT), and GLUT-4 levels in different visceral fat pad depots (epididymal -eWAT- and retroperitoneal -rWAT- adipose tissues) of SRD-fed rats. Results showed that chia seed reduces adipocytes hypertrophy, the increased lipid content and collagen deposition in both WAT. These changes were accompanied by a significant reduction of HSL and ATGL protein levels in eWAT and HSL protein levels in rWAT. Moreover, chia seed restored the altered expression pattern of the pAKT observed in SRD-fed rats, and modulated GLUT-4 levels. Chia seed could be a dietary intervention of great relevance with potential beneficial effects in the management of body fat excess and WAT function.
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Affiliation(s)
- Victoria Aiassa
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina
| | - María Del Rosario Ferreira
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - Noelia Villafañe
- Departamento de Morfología. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina
| | - María Eugenia D'Alessandro
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
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13
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Qi L, Zushin PJ, Chang CF, Lee YT, Alba DL, Koliwad S, Stahl A. Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell-Derived White Adipose Tissue Microphysiological Systems. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2103157. [PMID: 34761526 PMCID: PMC8776615 DOI: 10.1002/smll.202103157] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 09/21/2021] [Indexed: 05/13/2023]
Abstract
Impaired white adipose tissue (WAT) function has been recognized as a critical early event in obesity-driven disorders, but high buoyancy, fragility, and heterogeneity of primary adipocytes have largely prevented their use in drug discovery efforts highlighting the need for human stem cell-based approaches. Here, human stem cells are utilized to derive metabolically functional 3D adipose tissue (iADIPO) in a microphysiological system (MPS). Surprisingly, previously reported WAT differentiation approaches create insulin resistant WAT ill-suited for type-2 diabetes mellitus drug discovery. Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsive iADIPO are derived. Through concomitant optimization of an iADIPO-MPS, it is abled to obtain WAT with more unilocular and significantly larger (≈40%) lipid droplets compared to iADIPO in 2D culture, increased insulin responsiveness of glucose uptake (≈2-3 fold), fatty acid uptake (≈3-6 fold), and ≈40% suppressing of stimulated lipolysis giving a dynamic range that is competent to current in vivo and ex vivo models, allowing to identify both insulin sensitizers and desensitizers.
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Affiliation(s)
- Lin Qi
- Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, California, 94720, USA
| | - Peter James Zushin
- Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, California, 94720, USA
| | - Ching-Fang Chang
- Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, California, 94720, USA
| | - Yue Tung Lee
- Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, California, 94720, USA
| | - Diana L. Alba
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of California, San Francisco; Diabetes Center, University of California, San Francisco, San Francisco, California 94143, USA
| | - Suneil Koliwad
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of California, San Francisco; Diabetes Center, University of California, San Francisco, San Francisco, California 94143, USA
| | - Andreas Stahl
- Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, California, 94720, USA
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Cui Y, Mo Z, Ji P, Zhong J, Li Z, Li D, Qin L, Liao Q, He Z, Guo W, Chen L, Wang Q, Dong G, Chen W, Xiao Y, Xing X. Benzene Exposure Leads to Lipodystrophy and Alters Endocrine Activity In Vivo and In Vitro. Front Endocrinol (Lausanne) 2022; 13:937281. [PMID: 35909554 PMCID: PMC9326257 DOI: 10.3389/fendo.2022.937281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
Benzene is a ubiquitous pollutant and mainly accumulates in adipose tissue which has important roles in metabolic diseases. The latest studies reported that benzene exposure was associated with many metabolic disorders, while the effect of benzene exposure on adipose tissue remains unclear. We sought to investigate the effect using in vivo and in vitro experiments. Male adult C57BL/6J mice were exposed to benzene at 0, 1, 10 and 100 mg/kg body weight by intragastric gavage for 4 weeks. Mature adipocytes from 3T3-L1 cells were exposed to hydroquinone (HQ) at 0, 1, 5 and 25 μM for 24 hours. Besides the routine hematotoxicity, animal experiments also displayed significant body fat content decrease from 1 mg/kg. Interestingly, the circulating non-esterified fatty acid (NEFA) level increased from the lowest dose (ptrend < 0.05). Subsequent analysis indicated that body fat content decrease may be due to atrophy of white adipose tissue (WAT) upon benzene exposure. The average adipocyte area of WAT decreased significantly even from 1 mg/kg with no significant changes in total number of adipocytes. The percentages of small and large adipocytes in WAT began to significantly increase or decrease from 1 mg/kg (all p < 0.05), respectively. Critical genes involved in lipogenesis and lipolysis were dysregulated, which may account for the disruption of lipid homeostasis. The endocrine function of WAT was also disordered, manifested as significant decrease in adipokine levels, especially the leptin. In vitro cell experiments displayed similar findings in decreased fat content, dysregulated critical lipid metabolism genes, and disturbed endocrine function of adipocytes after HQ treatment. Pearson correlation analysis showed positive correlations between white blood cell (WBC) count with WAT fat content and plasma leptin level (r = 0.330, 0.344, both p < 0.05). This study shed light on the novel aspect that benzene exposure could induce lipodystrophy and disturb endocrine function of WAT, and the altered physiology of WAT might in turn affect benzene-induced hematotoxicity and metabolic disorders. The study provided new insight into understanding benzene-induced toxicity and the relationship between benzene and adipose tissue.
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Affiliation(s)
- Ying Cui
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Ziying Mo
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Penglei Ji
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Jingyi Zhong
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Zongxin Li
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Daochuan Li
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Lina Qin
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Qilong Liao
- Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Zhini He
- School of Public Health, Food Safety and Health Research Center, Southern Medical University, Guangzhou, China
| | - Wei Guo
- State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan and Center for Life Science, School of Life Sciences, Yunnan University, Kunming, China
| | - Liping Chen
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Qing Wang
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Guanghui Dong
- Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Wen Chen
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Yongmei Xiao
- Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Xiumei Xing
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Xiumei Xing,
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15
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Wu C, Chen X. Association of Serum Nonesterified Fatty Acids with Cardiovascular Event in Patients with Chronic Kidney Disease. Int J Gen Med 2021; 14:2033-2040. [PMID: 34079342 PMCID: PMC8164389 DOI: 10.2147/ijgm.s309595] [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: 03/04/2021] [Accepted: 04/09/2021] [Indexed: 11/23/2022] Open
Abstract
Background Chronic kidney disease (CKD) has been suggested to be associated with a high risk of cardiovascular diseases (CVD). The study aimed to evaluate the prognostic significance of nonesterified fatty acid (NEFA), also well known as free fatty acid, on predicting cardiovascular events in patients with CKD. Methods A total of 957 hospitalized patients with CKD in a stable clinical condition were enrolled at baseline. Then, the serum NEFA levels were measured. These included patients were prospectively followed up for a median of 10.2 years (range=0.4–11.5 years). We assessed whether serum NEFA levels at baseline can predict cardiovascular event during the follow-up. Results A total of 278 (29.1%) patients experienced cardiovascular events during follow-up. The Kaplan–Meier curve demonstrated that patients with higher serum NEFA levels (≥19.8 mg/dl) had a higher rate of cardiovascular events than patients with lower NEFA levels (<19.8 mg/dl). Multivariate Cox regression analysis suggested that elevated serum NEFA levels (HR=1.62; 95% CI 1.40–2.16, P<0.001) were independently associated with increased risk of cardiovascular events after correction for clinical confounding factors. Conclusion Elevated serum NEFA levels were associated with higher risk of cardiovascular events and may be a new parameter predicting cardiovascular events in patients with CKD, which may strengthen its potential effect in clinical practice.
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Affiliation(s)
- Chentang Wu
- Department of Cardiovascular Medicine, Mindong Hospital of Fujian Medical University, Fuan, Fujian, 355000, People's Republic of China
| | - Xueyun Chen
- Department of Endocrinology, Mindong Hospital of Fujian Medical University, Fuan, Fujian, 355000, People's Republic of China
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Zhu B, Zhang J, Zheng Q, Dong B, Wang M, Liu J, Cao Y. Free Fatty Acid is a Promising Biomarker in Triage Screening for Patients with Colorectal Cancer: A Case-Control Study. Cancer Manag Res 2021; 13:3749-3759. [PMID: 34007210 PMCID: PMC8123087 DOI: 10.2147/cmar.s307753] [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: 02/21/2021] [Accepted: 04/09/2021] [Indexed: 12/16/2022] Open
Abstract
Purpose The aim of our study was to identify the diagnostic ability of free fatty acids (FFAs) in younger colorectal cancer (CRC) patients by comparing carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Methods Patients screened for CRC at Fujian Medical University Union Hospital from January 2011 to December 2014 were recruited. Patients pathologically diagnosed with CRC or colorectal adenoma (CA) and healthy control participants were included. The enzyme endpoint method was applied to measure FFA levels. Receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of FFAs. Results FFA levels in late-stage patients (tumour-node-metastasis (TNM) stages III-IV) were higher than those in early-stage patients (TNM stages I-II) (P=0.02). The FFA levels in CRC patients were higher than those in controls of all ages, those younger than 50 years, males and females (P<0.001), and this difference was larger for patients younger than 50 years and females than for the all ages group. There was no significant difference in the FFA level between CA patients and healthy participants (P=0.53). The area under the curve (AUC) values of FFA, CEA, CA19-9, FFA+CEA, FFA+CA19-9 and FFA+CEA+CA19-9 distinguished CRC patients from controls at all ages, with values of 0.604, 0.731, 0.640, 0.754, 0.678 and 0.758, respectively; however, in the younger CRC patients (age≤50), the AUC values were 0.701, 0.735, 0.669, 0.798, 0.749, and 0.801. The AUC in female patients younger than 50 years was larger than that in males (0.769 vs 0.660), and this value was greater than the value for CEA in males (0.739) and females (0.729). Conclusion The FFA level not only can complement the predictive ability of the CEA and CA19-9 levels but also has a superior predictive ability in female and younger patients with CRC. FFA levels may have a potential role in triage screening of early CRC.
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Affiliation(s)
- Bin Zhu
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China
| | - Junrong Zhang
- Department of Emergency Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China
| | - Qingzhu Zheng
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China
| | - Binhua Dong
- Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People's Republic of China
| | - Meihua Wang
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China
| | - Jin Liu
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China
| | - Yingping Cao
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China
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Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis. Aging (Albany NY) 2021; 13:10891-10919. [PMID: 33864446 PMCID: PMC8109068 DOI: 10.18632/aging.202978] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 03/27/2021] [Indexed: 02/06/2023]
Abstract
Alzheimer’s disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife increases AD risk. Furthermore, AD is associated with diabetes-like alterations in glucose metabolism. Here, we investigated metabolic features of amyloid precursor protein overexpressing APP23 female mice modeling AD upon long-term challenge with high-sucrose (HSD) or high-fat diet (HFD). Compared to wild type littermates (WT), APP23 females were less prone to mild HSD-induced and considerable HFD-induced glucose tolerance deterioration, despite unaltered glucose tolerance during normal-control diet. Indirect calorimetry revealed increased energy expenditure and hyperactivity in APP23 females. Dietary interventions, especially HFD, had weaker effects on lean and fat mass gain, steatosis and adipocyte hypertrophy of APP23 than WT mice, as shown by 1H-magnetic-resonance-spectroscopy, histological and biochemical analyses. Proteome analysis revealed differentially regulated expression of mitochondrial proteins in APP23 livers and brains. In conclusion, hyperactivity, increased metabolic rate, and global mitochondrial dysfunction potentially add up to the development of AD-related body weight changes in APP23 females, becoming especially evident during diet-induced metabolic challenge. These findings emphasize the importance of translating this metabolic phenotyping into human research to decode the metabolic component in AD pathogenesis.
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Circulating Non-Esterified Fatty Acids as Biomarkers for Fat Content and Composition in Pigs. Animals (Basel) 2021; 11:ani11020386. [PMID: 33546411 PMCID: PMC7913534 DOI: 10.3390/ani11020386] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 12/16/2022] Open
Abstract
Simple Summary Circulating non-esterified fatty acids (NEFA) may be valuable as biomarkers for intramuscular fat content and fatty acid composition, as well as for other meat quality traits, in finishing heavy Duroc pigs. However, circulating NEFA composition may be affected by other factors such as age, fasting duration, and genetic variants related with adipogenesis and fatty acid metabolism pathways (e.g., SCD and LEPR). This study revealed that the circulating NEFA composition, especially the oleic acid content, reflects the metabolic status of an animal at a given time but has limited value as biomarker of intramuscular fat content and fatty acid composition. Abstract Circulating non-esterified fatty acids (NEFA) can reflect the composition of dietary fat or adipose tissues depending on the fasting conditions. Therefore, circulating NEFA may be valuable as biomarkers for meat quality traits, such as intramuscular fat content and fatty acid composition in finishing pigs. Genetic variants that regulate lipid metabolism can also modulate the circulating NEFA. We conducted an experiment with 150 heavy Duroc pigs to evaluate fluctuations in the circulating NEFA composition due to age, fasting duration and two genetic polymorphisms, one in the leptin receptor (LEPR; rs709596309) and one in the stearoyl-CoA desaturase (SCD; rs80912566) gene. Circulating NEFA were more saturated and less monounsaturated than the subcutaneous and intramuscular adipose tissues. Absolute circulating NEFA content was more influenced by fasting duration than age. The SCD polymorphism did not impact NEFA content or composition. The LEPR polymorphism affected the content but not the fatty acid composition. Circulating oleic acid NEFA content after a short fasting was positively correlated with intramuscular fat content and, after a long fasting, with intramuscular oleic acid content. We conclude that circulating NEFA reflect environmental and genetic metabolic changes but are of limited value as biomarkers for intramuscular fat content and fatty acid composition.
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Geng N, Luo Y, Cao R, Song X, Li F, Wang F, Gong Y, Xing L, Zhang H, Chen J. Effect of short-chain chlorinated paraffins on metabolic profiling of male SD rats. THE SCIENCE OF THE TOTAL ENVIRONMENT 2021; 750:141404. [PMID: 33182165 DOI: 10.1016/j.scitotenv.2020.141404] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 07/29/2020] [Accepted: 07/30/2020] [Indexed: 06/11/2023]
Abstract
The toxic effect of high-dose of short-chain chlorinated paraffins (SCCPs) has been extensively studied, however the possible health risks induced by SCCPs at low-dose remain largely unknown. In this study, a comprehensive toxicology analysis of SCCPs was conducted with the exposure levels from the environmental dose to the Lowest Observed Adverse Effect Level (LOAEL) of 100 mg/kg/day. General toxicology analysis revealed inconspicuous toxicity of the environmental dose of SCCPs, high dose SCCP exposure inhibited the growth rate and increased the liver weight of rat. Metabolomics analysis indicated that SCCP-induced toxicity was triggered at environmentally relevant doses. First, inhibition of energy metabolism was observed with the decrease in blood glucose and the dysfunction of TCA cycle, which may have contributed to lower body weight gain in rats exposed to a high dose of SCCPs. Second, the increase of free fatty acids indicated the acceleration of lipid metabolism to compensate for the energy deficiency caused by hypoglycemia. Lipid oxidative metabolism inevitably leads to oxidative stress and stimulates the up-regulation of antioxidant metabolites such as GSH and GSSH. The up-regulation of polyunsaturated fatty acids (PUFAs) and phospholipids composed of arachidonic acid indicates the occurrence of inflammation. Dysfunction of lipid metabolism can be an indicator of SCCP-induced liver injury.
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Affiliation(s)
- Ningbo Geng
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China
| | - Yun Luo
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Rong Cao
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China
| | - Xiaoyao Song
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China
| | - Fang Li
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Feidi Wang
- Institute of Quality and Standard for Agro-Products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Yufeng Gong
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China
| | - Liguo Xing
- Safety Evaluation Center of Shenyang Research Institute of Chemical Industry Ltd, Shenyang 110021, China
| | - Haijun Zhang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China
| | - Jiping Chen
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
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Regulatory Roles of SREBF1 and SREBF2 in Lipid Metabolism and Deposition in Two Chinese Representative Fat-Tailed Sheep Breeds. Animals (Basel) 2020; 10:ani10081317. [PMID: 32751718 PMCID: PMC7460493 DOI: 10.3390/ani10081317] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/22/2020] [Accepted: 07/27/2020] [Indexed: 11/22/2022] Open
Abstract
Simple Summary Sterol regulatory element binding proteins (SREBPs) play the crucial role in regulating the cholesterol and fatty acid metabolism. However, it is unclear whether SREBPs are involved in the regulation of lipid metabolism in fat-tailed sheep. This study reveals the expression profiles of SREBF1 and SREBF2 in liver and adipose tissues of two Chinese representative fat-tailed sheep breeds, and provides a new insight for the regulatory role of SREBP1 and SREBP2 in fat metabolism and deposition in fat-tailed sheep. Abstract Sterol regulatory element binding proteins (SREBPs) can regulate the lipid homeostasis by regulating its target genes, which are crucial for the cholesterol and fatty acid metabolism. However, the transcriptional regulation role of SREBPs in fat-tailed sheep is unclear. In this study, two Chinese representative breeds of total 80 fat-tailed sheep were employed, serum triglyceride, total cholesterol (TC), non-esterified fatty acid (NEFA), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and mRNA expressions of SREBF1 and SREBF2 in seven different adipose tissues and liver were examined in sheep at the ages of 4, 6, 8, 10, and 12 months, respectively. The subcellular localization and function of SREBP1/2 were predicted through bioinformatics approaches. The results demonstrated that serum TC and NEFA levels among breeds were significantly different, and most serum indices were dynamically altered in an age-dependent manner. The mRNA expression profiling of SREBF1 and SREBF2 are breed-specific with temporal and spatial expressions differences. Further analysis shows that SREBF1/2 transcriptional levels and tail traits are closely related. All investigations simplify that SREBF1/2 play a crucial role in lipid metabolism and deposition during growth and development of the fat-tailed sheep, which also provides a novel insight for revealing the genetic mechanism of different tail type and meat quality.
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21
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Nomura SO, Karger AB, Weir NL, Duprez DA, Tsai MY. Free fatty acids, cardiovascular disease, and mortality in the Multi-Ethnic Study of Atherosclerosis. J Clin Lipidol 2020; 14:531-541. [PMID: 32651087 DOI: 10.1016/j.jacl.2020.06.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 06/04/2020] [Accepted: 06/08/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Fasting free fatty acid (FFA) levels may be associated with cardiovascular disease (CVD) and mortality, but research among generally healthy adults, females, and racially/ethnically diverse populations is lacking. OBJECTIVE The primary aim of this project was to investigate prospective associations between fasting FFAs and coronary heart disease (CHD) and CVD incidence and CVD-specific and all-cause mortality in a generally healthy age, sex, and racially/ethnically heterogeneous population. METHODS This study was conducted in the Multi-Ethnic Study of Atherosclerosis cohort using baseline (2000-2002) fasting FFAs and outcome data through 2015 (N = 6678). Cox proportional hazards regression was used to calculate hazard ratios for associations between FFAs and CHD, CVD, CVD-specific mortality, and all-cause mortality. Interactions by age, sex, race/ethnicity, and metabolic syndrome were evaluated by stratification and cross-product terms. A secondary analysis was conducted to evaluate associations between FFAs, and inflammatory and endothelial activation biomarkers were evaluated using linear regression (analytic N range: 964-6662). RESULTS FFA levels were not associated with CHD or CVD incidence. Higher FFAs were associated with CVD-specific and all-cause mortality, but associations were attenuated in fully adjusted models with a borderline significant association remaining only for all-cause mortality (fully adjusted, per standard deviation increase hazard ratio = 1.07, 95% confidence interval: 1.00-1.14). Associations did not differ by age, sex, race/ethnicity, or metabolic syndrome. CONCLUSIONS Fasting FFAs were not associated with CHD, CVD, or CVD-specific mortality and were modestly associated with all-cause mortality, regardless of age, sex, race/ethnicity, or metabolic syndrome status.
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Affiliation(s)
- Sarah O Nomura
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
| | - Amy B Karger
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
| | - Natalie L Weir
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
| | - Daniel A Duprez
- Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Michael Y Tsai
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
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22
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Begaye B, Vinales KL, Hollstein T, Ando T, Walter M, Bogardus C, Krakoff J, Piaggi P. Impaired Metabolic Flexibility to High-Fat Overfeeding Predicts Future Weight Gain in Healthy Adults. Diabetes 2020; 69:181-192. [PMID: 31712321 PMCID: PMC6971489 DOI: 10.2337/db19-0719] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Accepted: 11/07/2019] [Indexed: 12/22/2022]
Abstract
The ability to switch fuels for oxidation in response to changes in macronutrient composition of diet (metabolic flexibility) may be informative of individuals' susceptibility to weight gain. Seventy-nine healthy, weight-stable participants underwent 24-h assessments of energy expenditure and respiratory quotient (RQ) in a whole-room calorimeter during energy balance (EBL) (50% carbohydrate, 30% fat) and then during 24-h fasting and three 200% overfeeding diets in a crossover design. Metabolic flexibility was defined as the change in 24-h RQ from EBL during fasting and standard overfeeding (STOF) (50% carbohydrate, 30% fat), high-fat overfeeding (HFOF) (60% fat, 20% carbohydrate), and high-carbohydrate overfeeding (HCOF) (75% carbohydrate, 5% fat) diets. Free-living weight change was assessed after 6 and 12 months. Compared with EBL, RQ decreased on average by 9% during fasting and by 4% during HFOF but increased by 4% during STOF and by 8% during HCOF. A smaller decrease in RQ, reflecting a smaller increase in lipid oxidation rate, during HFOF but not during the other diets predicted greater weight gain at both 6 and 12 months. An impaired metabolic flexibility to acute HFOF can identify individuals prone to weight gain, indicating that an individual's capacity to oxidize dietary fat is a metabolic determinant of weight change.
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Affiliation(s)
- Brittany Begaye
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ
| | - Karyne L Vinales
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ
- Endocrinology Division, Medicine Department, Phoenix VA Health Care System, Phoenix, AZ
| | - Tim Hollstein
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ
| | - Takafumi Ando
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ
| | - Mary Walter
- Clinical Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| | - Clifton Bogardus
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ
| | - Jonathan Krakoff
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ
| | - Paolo Piaggi
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ
- Department of Information Engineering, University of Pisa, Pisa, Italy
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23
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Zhang L, Han L, He J, Lv J, Pan R, Lv T. A high serum-free fatty acid level is associated with cancer. J Cancer Res Clin Oncol 2019; 146:705-710. [PMID: 31773260 PMCID: PMC7039835 DOI: 10.1007/s00432-019-03095-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 11/21/2019] [Indexed: 12/24/2022]
Abstract
PURPOSE The objectives of this work were to investigate whether the serum-free fatty acid (FFA) level is meaningful in cancer patients and its role in cancer diagnosis. METHODS A total of 2206 patients were divided into a cancer group (n = 1019) and a noncancer group (n = 1187). Age, sex, body mass index (BMI), and serum FFA and serum albumin levels were collected. Cancer patients were divided into subgroups according to the location of the cancer. We then compared serum FFA levels among the tumor subgroups. A receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of the FFA level. SPSS 22.0 software was used to analyze the results. RESULTS The FFA level was higher in the cancer group than in the noncancer group. According to the multivariate analysis, there was also an increased risk of cancer associated with a high FFA level after adjusting for old age, female sex, and a low BMI. In the subgroup analysis, the FFA level in patients with lung cancer, gastric cancer, thyroid cancer, rectal cancer, colon cancer, and ovarian cancer was significantly higher than that in noncancer patients. The area under the effect-time curve (AUC) of FFAs in the whole cancer group was 0.58, while the thyroid cancer, rectal cancer, and ovarian cancer subgroups had AUCs > 0.6. CONCLUSION Our study provides clinical evidence to support that fatty acid metabolism is associated with cancers and demonstrates that a high FFA level in the serum may be an indicator of cancer.
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Affiliation(s)
- Lili Zhang
- Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Lei Han
- Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Juan He
- Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Jing Lv
- Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Rongfang Pan
- Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Teng Lv
- Department of Gynaecology, The Affiliated Hospital of Qingdao University, 1677, Wutaishan Road, Xihaian District, Qingdao, 266000, China.
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Chen Y, Yu CY, Deng WM. The role of pro-inflammatory cytokines in lipid metabolism of metabolic diseases. Int Rev Immunol 2019; 38:249-266. [PMID: 31353985 DOI: 10.1080/08830185.2019.1645138] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Adipose tissue has been considered as a crucial source of certain pro-inflammatory cytokines; conversely, these pro-inflammatory cytokines are involved in regulating the proliferation and apoptosis of adipocytes, promoting lipolysis, inhibiting lipid synthesis and decreasing blood lipids, etc. In recent decades, extensive studies have indicated that pro-inflammatory cytokines play important roles in the development of lipid metabolism of metabolic diseases, including obesity, atherosclerosis, steatohepatitis and hyperlipoproteinemia. However, the involved pro-inflammatory cytokines types and the underlying mechanisms remain largely unknown. The "re-discovery" of cancer as a metabolic disorder largely occurred in the last five years. Although pro-inflammatory cytokines have been intensively investigated in cancer research, there are very few studies about the roles of pro-inflammatory cytokines in the lipid metabolism of cancer. In the current review, we provide an overview of the progress that has been made in the roles of different pro-inflammatory cytokines in lipid metabolism of metabolic diseases including cancer.
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Affiliation(s)
- Yan Chen
- Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Diseases and Microenvironment of Ministry of Education of China, Tianjin Medical University, Tianjin, China
| | - Chun-Yan Yu
- Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Diseases and Microenvironment of Ministry of Education of China, Tianjin Medical University, Tianjin, China
| | - Wei-Min Deng
- Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Diseases and Microenvironment of Ministry of Education of China, Tianjin Medical University, Tianjin, China
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25
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Hafidi ME, Buelna-Chontal M, Sánchez-Muñoz F, Carbó R. Adipogenesis: A Necessary but Harmful Strategy. Int J Mol Sci 2019; 20:ijms20153657. [PMID: 31357412 PMCID: PMC6696444 DOI: 10.3390/ijms20153657] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 07/16/2019] [Accepted: 07/20/2019] [Indexed: 02/06/2023] Open
Abstract
Obesity is considered to significantly increase the risk of the development of a vast range of metabolic diseases. However, adipogenesis is a complex physiological process, necessary to sequester lipids effectively to avoid lipotoxicity in other tissues, like the liver, heart, muscle, essential for maintaining metabolic homeostasis and has a crucial role as a component of the innate immune system, far beyond than only being an inert mass of energy storage. In pathophysiological conditions, adipogenesis promotes a pro-inflammatory state, angiogenesis and the release of adipokines, which become dangerous to health. It results in a hypoxic state, causing oxidative stress and the synthesis and release of harmful free fatty acids. In this review, we try to explain the mechanisms occurring at the breaking point, at which adipogenesis leads to an uncontrolled lipotoxicity. This review highlights the types of adipose tissue and their functions, their way of storing lipids until a critical point, which is associated with hypoxia, inflammation, insulin resistance as well as lipodystrophy and adipogenesis modulation by Krüppel-like factors and miRNAs.
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Affiliation(s)
- Mohammed El Hafidi
- Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
| | - Mabel Buelna-Chontal
- Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
| | - Fausto Sánchez-Muñoz
- Departamento de Inmunología, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
| | - Roxana Carbó
- Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico.
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26
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Hirata BKS, Cruz MM, de Sá RDCC, Farias TSM, Machado MMF, Bueno AA, Alonso-Vale MIC, Telles MM. Potential Anti-obesogenic Effects of Ginkgo biloba Observed in Epididymal White Adipose Tissue of Obese Rats. Front Endocrinol (Lausanne) 2019; 10:284. [PMID: 31133986 PMCID: PMC6523993 DOI: 10.3389/fendo.2019.00284] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 04/18/2019] [Indexed: 12/26/2022] Open
Abstract
Exacerbated expansion of adipose tissue seen in diet-induced obesity leads to endocrine dysfunction and disturbance in adipokine secretion, with such abnormal profile positively associated with type 2 diabetes and other mild chronic inflammatory conditions. Ginkgo biloba extract (GbE), a mixture of polyphenols with antioxidant properties, has been recently investigated in a variety of experimental models of endocrine dysfunction, with several potentially beneficial effects identified, including improvement in insulin sensitivity in obese rats, and reduction of weight gain in ovariectomy-induced obesity and diet-induced obesity. The aim of this study was to investigate in high fat diet-induced obese male rats the effects of GbE supplementation for 2 weeks on adipocyte volume and adipose tissue lipid accumulation. GbE supplementation was effective in reducing energy intake in obese rats compared to the saline-treated placebo group. Epididymal adipocyte volume was reduced in GbE-supplemented rats, as were epididymal [1-14C]-acetate incorporation into fatty acids, perilipin (Plin 1) and fatty acid synthase (Fasn) mRNA, and FAS protein levels. Adipocyte hypertrophy in obesity is associated with insulin resistance, and in the present study we observed a reduction in the adipocyte volume of GbE-supplemented obese rats to dimensions equivalent to adipocytes from non-obese rats. GbE supplementation significantly reduced acetate accumulation and tended to reduce [3H]-oleate incorporation, into epididymal adipose tissue, suggesting a potentially anti-obesogenic effect in longer term therapies. Further studies that investigate the effects of GbE supplementation in other experimental models are required to fully elucidate its suggested beneficial effects on mild chronic inflammatory conditions.
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Affiliation(s)
- Bruna K. S. Hirata
- Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, Brazil
| | - Maysa M. Cruz
- Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, Brazil
| | - Roberta D. C. C. de Sá
- Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, Brazil
| | - Talita S. M. Farias
- Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, Brazil
| | - Meira M. F. Machado
- Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, Brazil
| | - Allain A. Bueno
- Department of Biological Sciences, College of Health, Life and Environmental Sciences, University of Worcester, Worcester, United Kingdom
| | - Maria Isabel C. Alonso-Vale
- Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, Brazil
| | - Monica M. Telles
- Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, Brazil
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27
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Distinct Roles for Peroxisomal Targeting Signal Receptors Pex5 and Pex7 in Drosophila. Genetics 2018; 211:141-149. [PMID: 30389805 DOI: 10.1534/genetics.118.301628] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 10/26/2018] [Indexed: 12/26/2022] Open
Abstract
Peroxisomes are ubiquitous membrane-enclosed organelles involved in lipid processing and reactive oxygen detoxification. Mutations in human peroxisome biogenesis genes (Peroxin, PEX, or Pex) cause developmental disabilities and often early death. Pex5 and Pex7 are receptors that recognize different peroxisomal targeting signals called PTS1 and PTS2, respectively, and traffic proteins to the peroxisomal matrix. We characterized mutants of Drosophila melanogaster Pex5 and Pex7 and found that adult animals are affected in lipid processing. Pex5 mutants exhibited severe developmental defects in the embryonic nervous system and muscle, similar to what is observed in humans with PEX5 mutations, while Pex7 fly mutants were weakly affected in brain development, suggesting different roles for fly Pex7 and human PEX7. Of note, although no PTS2-containing protein has been identified in Drosophila, Pex7 from Drosophila can function as a bona fide PTS2 receptor because it can rescue targeting of the PTS2-containing protein thiolase to peroxisomes in PEX7 mutant human fibroblasts.
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28
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Coverdale JPC, Katundu KGH, Sobczak AIS, Arya S, Blindauer CA, Stewart AJ. Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding. Prostaglandins Leukot Essent Fatty Acids 2018; 135:147-157. [PMID: 30103926 PMCID: PMC6109191 DOI: 10.1016/j.plefa.2018.07.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 07/17/2018] [Accepted: 07/17/2018] [Indexed: 02/06/2023]
Abstract
Myocardial ischemia is difficult to diagnose effectively with still few well-defined biochemical markers for identification in advance, or in the absence of myocardial necrosis. "Ischemia-modified albumin" (IMA), a form of albumin displaying reduced cobalt-binding affinity, is significantly elevated in ischemic patients, and the albumin cobalt-binding (ACB) assay can measure its level indirectly. Elucidating the molecular mechanism underlying the identity of IMA and the ACB assay hinges on understanding metal-binding properties of albumin. Albumin binds most metal ions and harbours four primary metal binding sites: site A, site B, the N-terminal site (NTS), and the free thiol at Cys34. Previous efforts to clarify the identity of IMA and the causes for its reduced cobalt-binding capacity were focused on the NTS site, but the degree of N-terminal modification could not be correlated to the presence of ischemia. More recent work suggested that Co2+ ions as used in the ACB assay bind preferentially to site B, then to site A, and finally to the NTS. This insight paved the way for a new consistent molecular basis of the ACB assay: albumin is also the main plasma carrier for free fatty acids (FFAs), and binding of a fatty acid to the high-affinity site FA2 results in conformational changes in albumin which prevent metal binding at site A and partially at site B. Thus, this review advances the hypothesis that high IMA levels in myocardial ischemia and many other conditions originate from high plasma FFA levels hampering the binding of Co2+ to sites A and/or B. This is supported by biophysical studies and the co-association of a range of pathological conditions with positive ACB assays and high plasma FFA levels.
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Affiliation(s)
| | - Kondwani G H Katundu
- School of Medicine, University of St Andrews, St Andrews, United Kingdom; College of Medicine, University of Malawi, Blantyre, Malawi
| | - Amélie I S Sobczak
- School of Medicine, University of St Andrews, St Andrews, United Kingdom
| | - Swati Arya
- School of Medicine, University of St Andrews, St Andrews, United Kingdom
| | | | - Alan J Stewart
- School of Medicine, University of St Andrews, St Andrews, United Kingdom.
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Patel V, Joharapurkar A, Kshirsagar S, Sutariya B, Patel M, Patel H, Pandey D, Patel D, Bahekar R, Jain M. Central administration of coagonist of GLP-1 and glucagon receptors improves dyslipidemia. Biomed Pharmacother 2018; 98:364-371. [DOI: 10.1016/j.biopha.2017.12.068] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2017] [Revised: 11/29/2017] [Accepted: 12/15/2017] [Indexed: 12/25/2022] Open
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30
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Muller T, Demizieux L, Troy-Fioramonti S, Gresti J, Pais de Barros JP, Berger H, Vergès B, Degrace P. Overactivation of the endocannabinoid system alters the antilipolytic action of insulin in mouse adipose tissue. Am J Physiol Endocrinol Metab 2017; 313:E26-E36. [PMID: 28325733 DOI: 10.1152/ajpendo.00374.2016] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 03/08/2017] [Accepted: 03/08/2017] [Indexed: 11/22/2022]
Abstract
Evidence has accumulated that obesity-related metabolic dysregulation is associated with overactivation of the endocannabinoid system (ECS), which involves cannabinoid receptor 1 (CB1R), in peripheral tissues, including adipose tissue (AT). The functional consequences of CB1R activation on AT metabolism remain unclear. Since excess fat mobilization is considered an important primary event contributing to the onset of insulin resistance, we combined in vivo and in vitro experiments to investigate whether activation of ECS could alter the lipolytic rate. For this purpose, the appearance of plasma glycerol was measured in wild-type and CB1R-/- mice after acute anandamide administration or inhibition of endocannabinoid degradation by JZL195. Additional experiments were conducted on rat AT explants to evaluate the direct consequences of ECS activation on glycerol release and signaling pathways. Treatments stimulated glycerol release in mice fasted for 6 h and injected with glucose but not in 24-h fasted mice or in CB1R-/-, suggesting that the effect was dependent on plasma insulin levels and mediated by CB1R. We concomitantly observed that Akt cascade activity was decreased, indicating an alteration of the antilipolytic action of insulin. Similar results were obtained with tissue explants exposed to anandamide, thus identifying CB1R of AT as a major target. This study indicates the existence of a functional interaction between CB1R and lipolysis regulation in AT. Further investigation is needed to test if the elevation of ECS tone encountered in obesity is associated with excess fat mobilization contributing to ectopic fat deposition and related metabolic disorders.
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Affiliation(s)
- Tania Muller
- Team Pathophysiology of Dyslipidemia, INSERM UMR1231 Lipids, Nutrition, Cancer, Université de Bourgogne Franche-Comté, Dijon, France
| | - Laurent Demizieux
- Team Pathophysiology of Dyslipidemia, INSERM UMR1231 Lipids, Nutrition, Cancer, Université de Bourgogne Franche-Comté, Dijon, France
| | - Stéphanie Troy-Fioramonti
- Team Pathophysiology of Dyslipidemia, INSERM UMR1231 Lipids, Nutrition, Cancer, Université de Bourgogne Franche-Comté, Dijon, France
| | - Joseph Gresti
- Team Pathophysiology of Dyslipidemia, INSERM UMR1231 Lipids, Nutrition, Cancer, Université de Bourgogne Franche-Comté, Dijon, France
| | - Jean-Paul Pais de Barros
- Jean-Paul Pais de Barros, Lipidomic Platform, INSERM UMR1231 Lipids, Nutrition, Cancer, Université de Bourgogne Franche-Comté, Dijon, France; and
| | - Hélène Berger
- Team Pathophysiology of Dyslipidemia, INSERM UMR1231 Lipids, Nutrition, Cancer, Université de Bourgogne Franche-Comté, Dijon, France
| | - Bruno Vergès
- Team Pathophysiology of Dyslipidemia, INSERM UMR1231 Lipids, Nutrition, Cancer, Université de Bourgogne Franche-Comté, Dijon, France
- Endocrinology, Diabetology Department, University Hospital of Dijon, Dijon, France
| | - Pascal Degrace
- Team Pathophysiology of Dyslipidemia, INSERM UMR1231 Lipids, Nutrition, Cancer, Université de Bourgogne Franche-Comté, Dijon, France;
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31
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Homer AR, Fenemor SP, Perry TL, Rehrer NJ, Cameron CM, Skeaff CM, Peddie MC. Regular activity breaks combined with physical activity improve postprandial plasma triglyceride, nonesterified fatty acid, and insulin responses in healthy, normal weight adults: A randomized crossover trial. J Clin Lipidol 2017; 11:1268-1279.e1. [PMID: 28673802 DOI: 10.1016/j.jacl.2017.06.007] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 06/07/2017] [Accepted: 06/07/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Compared with prolonged sitting, regular activity breaks immediately lower postprandial glucose and insulin, but not triglyceride responses. Postprandial triglycerides can be lowered by physical activity but the effect is often delayed by ∼12 to 24 hours. OBJECTIVE The objective of the study was to determine whether regular activity breaks affect postprandial triglyceride response in a delayed manner similar to physical activity. METHODS In a randomized crossover trial, 36 adults (body mass index 23.9 kg/m2 [standard deviation 3.9]) completed four 2-day interventions: (1) prolonged sitting (SIT); (2) prolonged sitting with 30 minutes of continuous walking (60% VO2max), at the end of Day 1 (SIT + PAD1); (3) Sitting with 2 minutes of walking (60% VO2max) every 30 minutes (RAB); (4) A combination of the continuous walking and regular activity breaks in 2 and 3 above (RAB + PAD1). Postprandial plasma triglyceride, nonesterified fatty acids, glucose, and insulin responses were measured in venous blood over 5 hours on Day 2. RESULTS Compared with SIT, both RAB (difference: -43.61 mg/dL·5 hours; 95% confidence interval [CI] -83.66 to -2.67; P = .035) and RAB + PAD1 (-65.86 mg/dL·5 hours; 95% CI -112.14 to -19.58; P = .005) attenuated triglyceride total area under the curve (tAUC). RAB + PAD1 produced the greatest reductions in insulin tAUC (-23%; 95% CI -12% to -31%; P < .001), whereas RAB resulted in the largest increase in nonesterified fatty acids (tAUC, 10.08 mg/dL·5 hours; 95% CI 5.60-14.84; P < .001). There was no effect on glucose tAUC (P = .290). CONCLUSIONS Postprandial triglyceride response is attenuated by regular activity breaks, when measured ∼24 hours after breaks begin. Combining regular activity breaks with 30 minutes of continuous walking further improves insulinemic and lipidemic responses.
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Affiliation(s)
- Ashleigh R Homer
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - Stephen P Fenemor
- School of Physical Education, Sport and Exercise Sciences, University of Otago, Dunedin, New Zealand
| | - Tracy L Perry
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - Nancy J Rehrer
- School of Physical Education, Sport and Exercise Sciences, University of Otago, Dunedin, New Zealand
| | - Claire M Cameron
- Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand
| | - C Murray Skeaff
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - Meredith C Peddie
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand.
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Wang R, Xi L, Kukreja RC. PDE5 Inhibitor Tadalafil and Hydroxychloroquine Cotreatment Provides Synergistic Protection against Type 2 Diabetes and Myocardial Infarction in Mice. J Pharmacol Exp Ther 2017; 361:29-38. [PMID: 28123046 PMCID: PMC5363764 DOI: 10.1124/jpet.116.239087] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 01/23/2017] [Indexed: 12/15/2022] Open
Abstract
Diabetes is associated with a high risk for ischemic heart disease. We have previously shown that phosphodiesterase 5 inhibitor tadalafil (TAD) induces cardioprotection against ischemia/ reperfusion (I/R) injury in diabetic mice. Hydroxychloroquine (HCQ) is a widely used antimalarial and anti-inflammatory drug that has been reported to reduce hyperglycemia in diabetic patients. Therefore, we hypothesized that a combination of TAD and HCQ may induce synergistic cardioprotection in diabetes. We also investigated the role of insulin-Akt-mammalian target of rapamycin (mTOR) signaling, which regulates protein synthesis and cell survival. Adult male db/db mice were randomized to receive vehicle, TAD (6 mg/kg), HCQ (50 mg/kg), or TAD + HCQ daily by gastric gavage for 7 days. Hearts were isolated and subjected to 30-minute global ischemia, followed by 1-hour reperfusion in Langendorff mode. Cardiac function and myocardial infarct size were determined. Plasma glucose, insulin and lipid levels, and relevant pancreatic and cardiac protein markers were measured. Treatment with TAD + HCQ reduced myocardial infarct size (17.4% ± 4.3% vs. 37.8% ± 4.9% in control group, P < 0.05) and enhanced the production of ATP. The TAD + HCQ combination treatment also reduced fasting blood glucose, plasma free fatty acids, and triglyceride levels. Furthermore, TAD + HCQ increased plasma insulin levels (513 ± 73 vs. 232 ± 30 mU/liter, P < 0.05) with improved insulin sensitivity, larger pancreatic β-cell area, and pancreas mass. Insulin-like growth factor-1 (IGF-1) levels were also elevated by TAD + HCQ (343 ± 14 vs. 262 ± 22 ng/ml, P < 0.05). The increased insulin/IGF-1 resulted in activation of downstream Akt/mTOR cellular survival pathway. These results suggest that combination treatment with TAD and HCQ could be a novel and readily translational pharmacotherapy for reducing cardiovascular risk factors and protecting against myocardial I/R injury in type 2 diabetes.
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Affiliation(s)
- Rui Wang
- Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University. Richmond, Virginia
| | - Lei Xi
- Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University. Richmond, Virginia
| | - Rakesh C Kukreja
- Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University. Richmond, Virginia
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Su M, Huang W, Zhu B. Acetylshikonin from Zicao Prevents Obesity in Rats on a High-Fat Diet by Inhibiting Lipid Accumulation and Inducing Lipolysis. PLoS One 2016; 11:e0146884. [PMID: 26771185 PMCID: PMC4714907 DOI: 10.1371/journal.pone.0146884] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Accepted: 12/24/2015] [Indexed: 02/06/2023] Open
Abstract
Various drugs have been developed to treat obesity, but these have undesirable secondary effects, and an efficient but non-toxic anti-obesity drug from natural sources is desired. This study investigated the anti-obesity effects and mechanisms of action of acetylshikonin (AS)—which is used in traditional Chinese medicine—in rats on a high-fat diet (HFD). Rats were fed a normal diet or an HFD; the latter group was received no treatment or were treated with 100, 300, or 900 mg/kg AS extract by intragastric administration for 6 weeks. In addition, 3T3-L1 adipocytes were treated with AS and the effects on adipogenesis and lipolysis were evaluated by western blot analysis of adipogenic transcription factors and lipid-metabolizing enzyme levels and the phosphorylation status of protein kinase (PK) A and hormone-sensitive lipase (HSL). AS prevented HFD-induced obesity including reduction in body weight, white adipose tissue content, liver mass, and serum triglyceride and free fatty acid levels in rats. It also suppressed the expression of adipogenic differentiation transcription factors and decreased the expression of the adipocyte-specific proteins HSL and adipose triglyceride lipase (ATGL). Furthermore, AS treatment induced lipolysis, leading to the release of glycerol and increased in PKA and HSL phosphorylation. These findings demonstrate that AS has anti-obesity effects in a rat model and may be a safe treatment for obesity in humans.
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Affiliation(s)
- Meiling Su
- Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Wendong Huang
- Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Banghao Zhu
- Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
- * E-mail:
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Furuhashi M, Saitoh S, Shimamoto K, Miura T. Fatty Acid-Binding Protein 4 (FABP4): Pathophysiological Insights and Potent Clinical Biomarker of Metabolic and Cardiovascular Diseases. CLINICAL MEDICINE INSIGHTS-CARDIOLOGY 2015; 8:23-33. [PMID: 25674026 PMCID: PMC4315049 DOI: 10.4137/cmc.s17067] [Citation(s) in RCA: 205] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 12/16/2014] [Accepted: 12/16/2014] [Indexed: 12/13/2022]
Abstract
Over the past decade, evidences of an integration of metabolic and inflammatory pathways, referred to as metaflammation in several aspects of metabolic syndrome, have been accumulating. Fatty acid-binding protein 4 (FABP4), also known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays an important role in the development of insulin resistance and atherosclerosis in relation to metaflammation. Despite lack of a typical secretory signal peptide, FABP4 has been shown to be released from adipocytes in a non-classical pathway associated with lipolysis, possibly acting as an adipokine. Elevation of circulating FABP4 levels is associated with obesity, insulin resistance, diabetes mellitus, hypertension, cardiac dysfunction, atherosclerosis, and cardiovascular events. Furthermore, ectopic expression and function of FABP4 in several types of cells and tissues have been recently demonstrated. Here, we discuss both the significant role of FABP4 in pathophysiological insights and its usefulness as a biomarker of metabolic and cardiovascular diseases.
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Affiliation(s)
- Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Shigeyuki Saitoh
- Department of Nursing, Division of Medical and Behavioral Subjects, Sapporo Medical University School of Health Sciences, Sapporo, Japan
| | | | - Tetsuji Miura
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
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Mita T, Furuhashi M, Hiramitsu S, Ishii J, Hoshina K, Ishimura S, Fuseya T, Watanabe Y, Tanaka M, Ohno K, Akasaka H, Ohnishi H, Yoshida H, Saitoh S, Shimamoto K, Miura T. FABP4 is secreted from adipocytes by adenyl cyclase-PKA- and guanylyl cyclase-PKG-dependent lipolytic mechanisms. Obesity (Silver Spring) 2015; 23:359-67. [PMID: 25521833 DOI: 10.1002/oby.20954] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Accepted: 10/05/2014] [Indexed: 11/05/2022]
Abstract
OBJECTIVE Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes, and elevated plasma FABP4 level is associated with obesity-mediated metabolic phenotype. Postprandial regulation and secretory signaling of FABP4 has been investigated. METHODS Time courses of FABP4 levels were examined during an oral glucose tolerance test (OGTT; n=53) or a high-fat test meal eating (n=35). Effects of activators and inhibitors of adenyl cyclase (AC)-protein kinase A (PKA) signaling and guanylyl cyclase (GC)-protein kinase G (PKG) signaling on FABP4 secretion from mouse 3T3-L1 adipocytes were investigated. RESULTS FABP4 level significantly declined after the OGTT or a high-fat meal eating, while insulin level was increased. Treatment with low and high glucose concentration or palmitate for 2 h did not affect FABP4 secretion from 3T3-L1 adipocytes. FABP4 secretion was increased by stimulation of lipolysis using isoproterenol, a β3 -adrenoceptor agonist (CL316243), forskolin, dibutyryl-cAMP and atrial natriuretic peptide, and the induced FABP4 secretion was suppressed by insulin or an inhibitor of PKA (H-89), PKG (KT5823) or hormone sensitive lipase (CAY10499). CONCLUSIONS FABP4 is secreted from adipocytes in association with lipolysis regulated by AC-PKA- and GC-PKG-mediated signal pathways. Plasma FABP4 level declines postprandially, and suppression of FABP4 secretion by insulin-induced anti-lipolytic signaling may be involved in this decline in FABP4 level.
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Affiliation(s)
- Tomohiro Mita
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan
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Xiong Z, Xu H, Huang X, Ärnlöv J, Qureshi AR, Cederholm T, Sjögren P, Lindholm B, Risérus U, Carrero JJ. Nonesterified fatty acids and cardiovascular mortality in elderly men with CKD. Clin J Am Soc Nephrol 2015; 10:584-91. [PMID: 25637632 DOI: 10.2215/cjn.08830914] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 01/06/2015] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND OBJECTIVES Although nonesterified fatty acids (NEFAs) are essential as energy substrate for the myocardium, an excess of circulating NEFAs can be harmful. This study aimed to assess plausible relationships between serum NEFA and mortality due to cardiovascular disease (CVD) in individuals with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a prospective cohort study from the third examination cycle of the Uppsala Longitudinal Study of Adult Men, a population-based survey of 1221 elderly men aged 70-71 years residing in Uppsala, Sweden. Data collection took place during 1991-1995. All participants had measures of kidney function; this study investigated 623 (51.7%) of these patients with manifest CKD (defined as either eGFR<60 ml/min per 1.73 m(2) or urine albumin excretion rate ≥20 µg/min). Follow-up for mortality was done from examination date until death or December 31, 2007. After a median follow-up of 14 years (interquartile range, 8-16.8), associations of NEFAs with mortality (related to all causes, CVD, ischemic heart disease [IHD], or acute myocardial infarction) were ascertained. RESULTS The median serum NEFA was 14.1 mg/dl (interquartile range, 11.3-17.8). No association was found with measures of kidney function. Diabetes and serum triglycerides were the only multivariate correlates of NEFA. During follow-up, 453 participants died, of which 209 deaths were due to CVD, including 88 IHD deaths, with 41 attributed to acute myocardial infarction (AMI). In fully adjusted covariates, serum NEFA was an independent risk factor for all-cause mortality (hazard ratio [HR] per log2 increase, 1.22; 95% confidence interval [95% CI], 1.00 to 1.48) and CVD-related death (HR, 1.51; 95% CI, 1.15 to 1.99), including both IHD (HR, 1.51; 95% CI, 1.00 to 2.32) and AMI mortality (HR, 2.08; 95% CI, 1.09 to 3.98). CONCLUSIONS Elevated serum NEFA associated with CVD mortality, and particularly with mortality due to AMI, in a homogeneous population of older men with moderate CKD.
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Affiliation(s)
- Zibo Xiong
- Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, and Division of Nephrology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Hong Xu
- Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, and
| | - Xiaoyan Huang
- Division of Nephrology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Johan Ärnlöv
- Molecular Epidemiology, Department of Medical Sciences, and School of Health and Social Studies, Dalarna University, Falun, Sweden
| | - Abdul Rashid Qureshi
- Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, and
| | - Tommy Cederholm
- Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; and
| | - Per Sjögren
- Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; and
| | - Bengt Lindholm
- Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, and
| | - Ulf Risérus
- Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; and
| | - Juan Jesús Carrero
- Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, and Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden;
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Effects of weight loss via high fat vs. low fat alternate day fasting diets on free fatty acid profiles. Sci Rep 2015; 5:7561. [PMID: 25557754 PMCID: PMC5378987 DOI: 10.1038/srep07561] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 11/26/2014] [Indexed: 01/09/2023] Open
Abstract
Cardiovascular disease risk is associated with excess body weight and elevated plasma free fatty acid (FFA) concentrations. This study examines how an alternate-day fasting (ADF) diet high (HF) or low (LF) in fat affects plasma FFA profiles in the context of weight loss, and changes in body composition and lipid profiles. After a 2-week weight maintenance period, 29 women (BMI 30-39.9 kg/m(2)) 25-65 years old were randomized to an 8-week ADF-HF (45% fat) diet or an ADF-LF (25% fat) diet with 25% energy intake on fast days and ad libitum intake on feed days. Body weight, BMI and waist circumference were assessed weekly and body composition was measured using dual x-ray absorptiometry (DXA). Total and individual FFA and plasma lipid concentrations were measured before and after weight loss. Body weight, BMI, fat mass, total cholesterol, LDL-C and triglyceride concentrations decreased (P < 0.05) in both groups. Total FFA concentrations also decreased (P < 0.001). In the ADF-LF group, decreases were found in several more FFAs than in the ADF-HF group. In the ADF-HF group, FFA concentrations were positively correlated with waist circumference. Depending on the macronutrient composition of a diet, weight loss with an ADF diet decreases FFA concentrations through potentially different mechanisms.
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Borer KT. Counterregulation of insulin by leptin as key component of autonomic regulation of body weight. World J Diabetes 2014; 5:606-629. [PMID: 25317239 PMCID: PMC4138585 DOI: 10.4239/wjd.v5.i5.606] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Revised: 05/15/2014] [Accepted: 06/03/2014] [Indexed: 02/05/2023] Open
Abstract
A re-examination of the mechanism controlling eating, locomotion, and metabolism prompts formulation of a new explanatory model containing five features: a coordinating joint role of the (1) autonomic nervous system (ANS); (2) the suprachiasmatic (SCN) master clock in counterbalancing parasympathetic digestive and absorptive functions and feeding with sympathetic locomotor and thermogenic energy expenditure within a circadian framework; (3) interaction of the ANS/SCN command with brain substrates of reward encompassing dopaminergic projections to ventral striatum and limbic and cortical forebrain. These drive the nonhomeostatic feeding and locomotor motivated behaviors in interaction with circulating ghrelin and lateral hypothalamic neurons signaling through melanin concentrating hormone and orexin-hypocretin peptides; (4) counterregulation of insulin by leptin of both gastric and adipose tissue origin through: potentiation by leptin of cholecystokinin-mediated satiation, inhibition of insulin secretion, suppression of insulin lipogenesis by leptin lipolysis, and modulation of peripheral tissue and brain sensitivity to insulin action. Thus weight-loss induced hypoleptimia raises insulin sensitivity and promotes its parasympathetic anabolic actions while obesity-induced hyperleptinemia supresses insulin lipogenic action; and (5) inhibition by leptin of bone mineral accrual suggesting that leptin may contribute to the maintenance of stability of skeletal, lean-body, as well as adipose tissue masses.
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The production of nitric oxide, IL-6, and TNF-alpha in palmitate-stimulated PBMNCs is enhanced through hyperglycemia in diabetes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2014; 2014:479587. [PMID: 24803982 PMCID: PMC3997868 DOI: 10.1155/2014/479587] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 03/01/2014] [Indexed: 01/22/2023]
Abstract
We examined nitric oxide (NO), IL-6, and TNF-α secretion from cultured palmitate-stimulated PBMNCs or in the plasma from type 2 diabetes mellitus (T2MD) patients or nondiabetic (ND) controls. Free fatty acids (FFA) have been suggested to induce chronic low-grade inflammation, activate the innate immune system, and cause deleterious effects on vascular cells and other tissues through inflammatory processes. The levels of NO, IL-6, TNF-α, and MDA were higher in supernatant of palmitate stimulated blood cells (PBMNC) or from plasma from patients. The results obtained in the present study demonstrated that hyperglycemia in diabetes exacerbates in vitro inflammatory responses in PBMNCs stimulated with high levels of SFA (palmitate). These results suggest that hyperglycemia primes PBMNCs for NO, IL-6, and TNF-alpha secretion under in vitro FFA stimulation are associated with the secretion of inflammatory biomarkers in diabetes. A combined therapy targeting signaling pathways activated by hyperglycemia in conjunction with simultaneous control of hyperglycemia and hypertriglyceridemia would be suggested for controlling the progress of diabetic complications.
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Shin YH, Jung HL, Ryu JW, Kim PS, Ha TY, An JY, Kang HY. Effects of a Pre-Exercise Meal on Plasma Growth Hormone Response and Fat Oxidation during Walking. Prev Nutr Food Sci 2014; 18:175-80. [PMID: 24471129 PMCID: PMC3892495 DOI: 10.3746/pnf.2013.18.3.175] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Accepted: 08/23/2013] [Indexed: 01/20/2023] Open
Abstract
The purpose of this study was to determine the effects of a pre-exercise meal on the plasma human growth hormone (hGH) response and fat oxidation during walking. Subjects (n=8) were randomly provided with either 1 g/kg body weight of glucose in 200 mL water (CHO) or 200 mL water alone (CON) 30 min prior to exercise and subsequently walked on a treadmill at 50% of VO2max for 60 min. Plasma hGH concentrations were significantly higher in subjects who received CHO compared to those who received CON at 15 and 30 min. The fat oxidation rate in the CHO was significantly lower than the CON while walking for 5~15, 25~35 and 45~55 min. Plasma FFA levels were also significantly lower in the CHO compared to the CON at 30, 45 and 60 min. Plasma glucose levels in the CHO were significantly lower while plasma insulin levels were significantly higher than in the CON at 15 and 30 min. Therefore, the results of this study suggest that the elevation of plasma hGH levels due to the intake of a pre-exercise meal may not be strongly related to fat oxidation and plasma free fatty acid (FFA) levels during low-intensity exercise.
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Affiliation(s)
- Young-Ho Shin
- Exercise Metabolism Laboratory, Kyungpook National University, Daegu 702-701, Korea
| | - Hyun-Lyung Jung
- Exercise Metabolism Laboratory, Kyungpook National University, Daegu 702-701, Korea
| | - Jong-Woo Ryu
- Exercise Metabolism Laboratory, Kyungpook National University, Daegu 702-701, Korea
| | - Pan-Soo Kim
- Department of Judo, Yong In University, Gyeonggi 449-714, Korea
| | - Tae-Yeol Ha
- Division of Metabolism and Functionality Research, Korea Food Research Institute, Gyeonggi 463-746, Korea
| | - Ji-Yoon An
- Division of Metabolism and Functionality Research, Korea Food Research Institute, Gyeonggi 463-746, Korea
| | - Ho-Youl Kang
- Exercise Metabolism Laboratory, Kyungpook National University, Daegu 702-701, Korea
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GARCIA-DIAZ DF, LOPEZ-LEGARREA P, QUINTERO P, MARTINEZ JA. Vitamin C in the Treatment and/or Prevention of Obesity. J Nutr Sci Vitaminol (Tokyo) 2014; 60:367-79. [DOI: 10.3177/jnsv.60.367] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
| | | | - Pablo QUINTERO
- Department of Gastroenterology, School of Medicine, Pontifical Catholic University of Chile
| | - Jose Alfredo MARTINEZ
- CIBERobn. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III
- Department of Food Sciences and Physiology, University of Navarra
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Roy VK, Kumar A, Joshi P, Arora J, Ahanger AM. Plasma free Fatty Acid concentrations as a marker for acute myocardial infarction. J Clin Diagn Res 2013; 7:2432-4. [PMID: 24392364 DOI: 10.7860/jcdr/2013/7682.3566] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Accepted: 09/27/2013] [Indexed: 11/24/2022]
Abstract
BACKGROUND Acute myocardial infarction carries a high mortality among cardiac patients.The discovery of the fact that certain enzymes like CPK, LDH liberated into circulation following necrosis of the myocardial cells came as boon for physicians and patients. There has been a constant search of different parameters for the diagnosis and management of CoronaryArtery Diseases (CAD). AIM The present study was undertaken to investigate a possible relation between the changes in plasma free fatty acid (FFA) concentration and acute myocardial infarction. MATERIAL AND METHODS Fifty cases (25 males and 25 females) of acute myocardial infarction were selected for the present study. All the patients were in the age group of 40-70 years. For the control group fifty (25 male and 25 female) subjects of same age group were selected from patient's relatives and friends. Plasma free fatty acid concentration was estimated by Titrametric method of Trout et al., (1960), a modified version of Dole (1956). STATISTICAL ANALYSIS The statistical analysis of the data of the present study was done by using SPSS, version 14.0.1 was used. RESULTS Our study showed a significant increase in plasma FFA in the first 24 hours of acute myocardial infarction with subsequent normalisation on the 7th day.The difference between the first and the seventh day was statistically significant. CONCLUSION The FFA were found raised in cases of acute myocardial infarction.On the basis of present study, it is worth to say that estimation of serum free fatty acid should be done routinely at the earliest opportunity in all cases of acute myocardial infarction.
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Affiliation(s)
- Vijay Kumar Roy
- Assistant Professor, Departement of Physiology, SGT Medical College, Hospital & Reaserch Institute , Budhera, Gurgaon-122505, Haryana, India
| | - Anil Kumar
- Assistant Professor, Departement of Physiology, SGT Medical College, Hospital & Reaserch Institute , Budhera, Gurgaon-122505, Haryana, India
| | - Prabal Joshi
- Associate Professor, Departement of Physiology, SGT Medical College, Hospital & Reaserch Institute , Budhera, Gurgaon-122505, Haryana, India
| | - Jyoti Arora
- Assistant Professor, Departement of Physiology, SGT Medical College, Hospital & Reaserch Institute , Budhera, Gurgaon-122505, Haryana, India
| | - Ali Mohammad Ahanger
- Professor and Head, Departement of Physiology, SGT Medical College, Hospital & Reaserch Institute , Budhera, Gurgaon-122505, Haryana, India
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Tinahones FJ, Garrido-Sánchez L, Murri M, García-Fuentes E, Cardona F. Particular characteristics of the metabolic syndrome in patients with morbid obesity. ACTA ACUST UNITED AC 2013; 60:127-35. [DOI: 10.1016/j.endonu.2012.09.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Revised: 09/08/2012] [Accepted: 09/12/2012] [Indexed: 10/27/2022]
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Abstract
Hypocaloric diet is a key component of the weight-reducing treatment of obesity and obesity-related disorders. Hypocaloric diets and the associated weight reduction promote improvement of metabolic profile of obese individuals. Among the mechanisms that underlie this beneficial metabolic outcome, the diet-induced modifications of morphological and functional characteristics of human adipose tissue (AT) are believed to have an important role. Prospective studies of hypocaloric weight-reducing dietary intervention demonstrate effects on adipocyte metabolism, namely lipolysis and lipogenesis, and associated changes of the adipocyte size. The endocrine function of AT, which involves cytokine and adipokine production by adipocytes, as well as by cells of stromavascular fraction, is also regulated by dietary intervention. Related inflammatory status of AT is modulated also as a consequence of the changes in recruitment of immune cells, mainly macrophages, in AT. Here, we give an overview of metabolic and endocrine modifications in human AT induced by a variety of hypocaloric diets.
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45
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Ozarda Y, Tuncer GO, Gunes Y, Eroz E. Serum levels of leptin, adiponectin and resistin are interrelated and related to total antioxidant capacity, free fatty acids and phospholipids in early neonatal life. Clin Biochem 2012; 45:298-302. [PMID: 22261091 DOI: 10.1016/j.clinbiochem.2011.12.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2011] [Revised: 12/19/2011] [Accepted: 12/22/2011] [Indexed: 02/02/2023]
Abstract
OBJECTIVES The aims of this study were to determine interrelationships between serum leptin, adiponectin and resistin, insulin-like growth factor-1 (IGF-1), total antioxidant capacity (TAC), non-esterified fatty acids (NEFA) and phospholipids concentrations in infants. DESIGN AND METHODS A cross-sectional study was conducted to assess serum levels of leptin, adiponectin, resistin, IGF-1, TAC, NEFA and phospholipids in 45 breast-fed infants enrolled at 4-30 days after birth. RESULTS Serum leptin and adiponectin concentrations were positively correlated. Serum resistin concentrations were inversely correlated to serum leptin and adiponectin concentrations. Serum TAC was positively correlated to serum leptin and adiponectin, and inversely to serum resistin concentrations. Serum adiponectin concentrations were positively related to serum NEFA and phospholipid concentrations. Serum resistin concentrations were inversely related to serum NEFA, and phospholipid concentrations. CONCLUSION These data show that circulatory levels of leptin, adiponectin and resistin are interrelated and they apparently interact with the anti-oxidant system of infants.
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Affiliation(s)
- Yesim Ozarda
- Department of Biochemistry, Uludag University Medical School, Bursa, Turkey.
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Azekoshi Y, Yasu T, Watanabe S, Tagawa T, Abe S, Yamakawa K, Uehara Y, Momomura S, Urata H, Ueda S. Free Fatty Acid Causes Leukocyte Activation and Resultant Endothelial Dysfunction Through Enhanced Angiotensin II Production in Mononuclear and Polymorphonuclear Cells. Hypertension 2010; 56:136-42. [DOI: 10.1161/hypertensionaha.110.153056] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Yoko Azekoshi
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
| | - Takanori Yasu
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
| | - Saiko Watanabe
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
| | - Tatsuya Tagawa
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
| | - Satomi Abe
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
| | - Ken Yamakawa
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
| | - Yoshinari Uehara
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
| | - Shinichi Momomura
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
| | - Hidenori Urata
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
| | - Shinichiro Ueda
- From the Department of Clinical Pharmacology and Therapeutics (Y.A., T.Y., S.W., T.T., K.Y., S.U.), University of the Ryukyus School of Medicine, Okinawa, Japan; Department of Cardiovascular Diseases (S.A., Y.U., H.U.), Fukuoka University Chikushi Hospital, Fukuoka, Japan; Department of First Integrated Medicine (S.M.), Saitama Medical Center, Jichi Medical University, Saitama, Japan; Current address (T.T.): Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin
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47
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Abstract
Structured exercise is considered an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in Type 2 diabetes. Current clinical guidelines acknowledge the therapeutic strength of exercise intervention. This paper reviews the wide pathophysiological problems associated with Type 2 diabetes and discusses the benefits of exercise therapy on phenotype characteristics, glycemic control and cardiovascular risk profile in Type 2 diabetes patients. Based on the currently available literature, it is concluded that Type 2 diabetes patients should be stimulated to participate in specifically designed exercise intervention programs. More attention should be paid to cardiovascular and musculoskeletal deconditioning as well as motivational factors to improve long-term treatment adherence and clinical efficacy. More clinical research is warranted to establish the efficacy of exercise intervention in a more differentiated approach for Type 2 diabetes subpopulations within different stages of the disease and various levels of co-morbidity.
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Affiliation(s)
- Stephan F E Praet
- Department of Rehabilitation Medicine, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands.
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48
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Warensjö E, Rosell M, Hellenius ML, Vessby B, De Faire U, Risérus U. Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance. Lipids Health Dis 2009; 8:37. [PMID: 19712485 PMCID: PMC2746208 DOI: 10.1186/1476-511x-8-37] [Citation(s) in RCA: 152] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2009] [Accepted: 08/27/2009] [Indexed: 11/10/2022] Open
Abstract
Fatty acid composition of serum lipids and adipose tissue triacylglycerols (AT-TAG) partly reflect dietary fatty acid intake. The fatty acid composition is, besides the diet, also influenced by desaturating enzymes that can be estimated using product-to-precursor fatty acid ratios. The interrelationships between desaturase indices derived from different serum lipid fractions and adipose tissue are unclear, as well as their associations with obesity and insulin resistance. We aimed to investigate cross-sectional correlations between desaturase indices as measured in serum lipid fractions (phospholipids; PL and free fatty acids; FFA) and in adipose tissue (AT-TAG). In a population-based sample of 301 healthy 60-year-old men various desaturase indices were assessed: stearoyl-CoA-desaturase (16:1n-7/16:0; SCD-16 and 18:1n-9/18:0; SCD-18, respectively), delta-6-desaturase (20:3n-6/18:2n-6; D6D) and delta-5-desaturase (20:4n-6/20:3n-6; D5D). Correlations with BMI and insulin resistance (HOMA-IR) were also examined. SCD-16 and D5D were significantly correlated between fractions and tissues (all r > 0.30), whereas SCD-18 and D6D were not. Desaturase indices in serum FFA and AT-TAG were significantly correlated; SCD-16 (r = 0.63), SCD-18 (r = 0.37), and D5D (r = 0.43). In phospholipids, SCD-16 was positively correlated to BMI (r = 0.15), while D5D negatively to both BMI (r = -0.30) and HOMA-IR (r = -0.31), all p < 0.01. D6D in both phospholipids and AT-TAG was positively correlated to HOMA-IR and BMI (all p < 0.01). In conclusion, SCD-1 and D5D activity indices showed overall strong correlations between lipid pools. SCD-1 activity index in adipose tissue is best reflected by 16:1/16:0-ratio in serum FFA, but associations with obesity and insulin resistance differ between these pools. D5D in PL was inversely related to obesity and insulin resistance, whereas D6D index showed positive associations.
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Affiliation(s)
- Eva Warensjö
- Department of Public Health and Caring Sciences, Clinical nutrition and metabolism, Uppsala University, Uppsala, Sweden.
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49
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The effects of dietary manipulation and exercise on weight loss and related indices of health in horses. COMPARATIVE EXERCISE PHYSIOLOGY 2009. [DOI: 10.1017/s1478061509356169] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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50
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Garcia-Diaz DF, Campion J, Milagro FI, Paternain L, Solomon A, Martinez JA. Ascorbic acid oral treatment modifies lipolytic response and behavioural activity but not glucocorticoid metabolism in cafeteria diet-fed rats. Acta Physiol (Oxf) 2009; 195:449-57. [PMID: 19040713 DOI: 10.1111/j.1748-1716.2008.01942.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
AIM To analyse the effects of vitamin C (VC), a potent dietary antioxidant, oral supplementation on body weight gain, behavioural activity, lipolytic response and glucocorticoid metabolism in the early stages of diet-induced overweight in rats. METHODS Food intake, locomotive activity and faecal corticosterone were assessed during the 14 day trial period. After 2 weeks, the animals were sacrificed and the body composition, biochemical markers and lipolytic response from isolated adipocytes from retroperitoneal white adipose tissue were examined. RESULTS The intake of a high-fat diet by rats induced a significant increase in body weight, adiposity and insulin resistance markers as well as a decrease in faecal corticosterone levels compared with standard diet-fed rats. Interestingly, the animals fed on the cafeteria diet showed a significant increase in the isoproterenol-induced lipolytic response in isolated adipocytes. Furthermore, this cafeteria-fed group showed a reduced locomotive behaviour than the control rats. On the other hand, oral VC supplementation in animals receiving the high-fat diet restored the cafeteria diet effect in some of the analysed variables such as final body weight and plasma insulin to control group levels. Remarkably, increases in locomotive behaviour and a significant decrease in the lipolytic response induced by isoproterenol on isolated adipocytes from animals treated with VC were observed. CONCLUSION This work demonstrates that an oral ascorbic acid supplementation has direct effects on behavioural activity and on adipocyte lipolysis in early obesity stages in rats, which could indicate a protective short-term role of this vitamin against adiposity induced by chronic high-fat diet consumption.
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Affiliation(s)
- D F Garcia-Diaz
- Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Pamplona, Spain
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