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Edward C Mun - One of the best experts on this subject based on the ideXlab platform.
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thyroid hormone related regulation of gene expression in human fatty liver
The Journal of Clinical Endocrinology and Metabolism, 2009Co-Authors: Jussi Pihlajamaki, Tanner Boes, Eun Young Kim, Farrell Dearie, Brian W Kim, Joshua Schroeder, Edward C MunAbstract:Context: Fatty liver is an important Complication of Obesity; however, regulatory mechanisms mediating altered gene expression patterns have not been identified. Objective: The aim of the study was to identify novel transcriptional changes in human liver that could contribute to hepatic lipid accumulation and associated insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis. Design: We evaluated gene expression in surgical liver biopsies from 13 obese (nine with type 2 diabetes) and five control subjects using Affymetrix U133A microarrays. PCR validation was performed in liver biopsies using an additional 16 subjects. We also tested thyroid hormone responses in mice fed chow or high-fat diet. Setting: Recruitment was performed in an academic medical center. Participants: Individuals undergoing elective surgery for Obesity or gallstones participated in the study. Results: The top-ranking gene set, down-regulated in obese subjects, was comprised of genes previously demonstrated to be positive...
Samuel Klein - One of the best experts on this subject based on the ideXlab platform.
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adipose tissue monomethyl branched chain fatty acids and insulin sensitivity effects of Obesity and weight loss
Obesity, 2015Co-Authors: Faidon Magkos, Dequan Zhou, Christopher J Eagon, Elisa Fabbrini, Adewole L Okunade, Samuel KleinAbstract:Insulin resistance is a common metabolic Complication of Obesity and an important risk factor for the development of type 2 diabetes, the metabolic syndrome, and coronary heart disease (1, 2). It has been proposed that an increase in circulating branched-chain amino acids (BCAA), valine, leucine, and isoleucine, is involved in the pathogenesis of insulin resistance, because increased plasma BCAA concentrations are often observed in obese and insulin resistant states (3, 4), and weight loss leads to decreased plasma BCAA concentrations and improved insulin action (5, 6). However, the underlying mechanism(s) responsible for the relationship between BCAA metabolism and insulin resistance is not known. Monomethyl branched chain fatty acids (mmBCFA) could provide a link between BCAA metabolism and metabolic dysfunction. In most peripheral tissues, BCAA are deaminated by mitochondrial branched chain aminotransferase (BCAT2 or BCATm) to generate branched-chain α-ketoacids (7), which are then decarboxylated by the branched-chain α-ketoacid dehydrogenase complex (8). The resulting short-chain branched acyl moieties can be exported out of mitochondria (9) and undergo conventional de novo fatty acid biosynthesis, catalyzed by fatty acid synthase (FAS), to produce mmBCFA (10). Alternatively, the fatty acyl chain could be extended within mitochondria by using the mitochondrial fatty acid synthesis (FAS II) system (11) (Supplementary Figure S1). The predominant branching in mmBCFA is near the terminal end of the carbon chain with an isopropyl or isobutyl group denoted as iso- or anteiso-BCFA, respectively. mmBCFA are present in a large range of organisms from bacteria to mammals, indicating conserved metabolic pathways for their synthesis and function. The enzymes involved in BCAA metabolism are key regulators of both the degradation of BCAA and the synthesis of mmBCFA. Skeletal muscle and adipose tissue are the primary sites for BCAA degradation (12), whereas BCAA catabolism in the liver is minimal because of low levels of BCATm (7). A study conducted in a rodent model demonstrated that adipose tissue BCAA metabolism can modulate circulating BCAA concentrations (13), presumably because adipose tissue is a major site for plasma BCAA uptake and conversion to lipids (14). Whole tissue assessments of BCAA catabolic activities and kinetics also suggest that adipose tissue could play an important role in regulating whole body BCAA homeostasis in people (15, 16). Adipose tissue gene expression of enzymes involved in BCAA catabolism is lower in obese and insulin resistant mice and people than in their lean counterparts (17, 18). Therefore, it is possible that increased catabolism of BCAA and conversion to mmBCFA in adipose tissue could improve insulin sensitivity by clearing BCAA from plasma. The purpose of the present study was to evaluate the possibility that adipose tissue mmBCFA metabolism is associated with whole-body (primarily skeletal muscle) insulin sensitivity in obese subjects. Accordingly, we conducted: i) a cross-sectional study to assess the relationship between adipose tissue mmBCFA content and insulin sensitivity in lean and obese subjects, and ii) a longitudinal study to assess the effects of marked weight loss on adipose tissue mmBCFA metabolism and insulin sensitivity.
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randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease
Hepatology, 2012Co-Authors: Shelby Sullivan, Erik P Kirk, Bettina Mittendorfer, Bruce W Patterson, Samuel KleinAbstract:Nonalcoholic fatty liver disease (NAFLD) is a common Complication of Obesity, and is associated with abnormalities in hepatic very-low-density lipoprotein (VLDL) metabolism and increased serum triglyceride (TG) concentration (1, 2). Lifestyle modification involving diet-induced weight loss and regular physical activity reduces intrahepatic triglyceride (IHTG) content and improves the metabolic derangements associated with NAFLD (3-17). Very small amounts of weight loss can cause marked decreases (20%-60%) in IHTG content (18-20). In fact, we have found that even 48 h of calorie restriction caused a 20% decrease in IHTG content in obese subjects (21). However, few studies have evaluated the effect of regular physical activity, independent of weight loss, on NAFLD. Current guidelines from the Department of Health and Human Services, the American College of Sports Medicine, and the American Heart Association, recommend that adults perform at least 150 min, but preferably 300 min of moderate-intensity physical activity per week; or at least 75 minutes, but preferably 150 minutes, of vigorous physical activity per week to achieve health benefits (22, 23). Data from two studies have recently shown that 4-12 weeks of vigorous intensity exercise training caused a small decrease in IHTG content (24, 25). However, obese people are more likely to adhere to a moderate intensity than a vigorous intensity exercise program (26), in part, because obese persons have lower levels of pleasure after high intensity exercise (27), and exercise intensity is perceived to be higher in obese than lean subjects (28). The potential benefits of regular moderate intensity exercise on IHTG content and hepatic metabolic function in obese people with NAFLD has not been carefully studied. The purpose of this study was to investigate the effect of the recommended exercise guidelines for moderate intensity endurance exercise training (150-300 min per week) on IHTG content and VLDL kinetics in obese subjects with NAFLD. We hypothesized that exercise training would result in decreased IHTG content and hepatic VLDL-TG and VLDL-apolipoprotein B-100 (apoB-100) secretion rates. Magnetic resonance spectroscopy (MRS) was used to assess IHTG content and stable isotopically labeled tracer techniques were used to assess VLDL-TG and VLDL-apoB-100 kinetics in our study subjects before and after 16 weeks of supervised exercise training.
D Boute - One of the best experts on this subject based on the ideXlab platform.
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obstructive sleep apnea syndrome a frequent Complication of Obesity
Biomedicine & Pharmacotherapy, 1994Co-Authors: J M Borys, D BouteAbstract:Obstructive sleep apnea syndrome (OSAS) is a major health problem, not only because of its consequences in terms of morbidity and mortality, but also because of its social impact in the form of car accidents and industrial accidents. These facts stress the necessity of screening OSAS among the population, particularly in patients suffering from Obesity or hypertension, diseases frequently associated with OSAS. This review will focus on the epidemiology and the pathophysiology of this syndrome, its clinical features with a view to screening OSAS, and the main examination used to confirm the diagnosis. The management of OSAS will be discussed.
Elizabeth M Brunt - One of the best experts on this subject based on the ideXlab platform.
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pathology of nonalcoholic fatty liver disease
Nature Reviews Gastroenterology & Hepatology, 2010Co-Authors: Elizabeth M BruntAbstract:Nonalcoholic fatty liver disease (NAFLD) is a significant Complication of Obesity and is recognized as the hepatic manifestation of the metabolic syndrome. The process occurs in adults and children and is characterized by the presence of increased amounts of fat in the liver (steatosis). With inflammation, cell death and scarring (fibrosis), the process may result in end-stage liver disease, or be a precursor for hepatocellular carcinoma. Excess hepatic fat is now recognized as an independent marker for increased cardiovascular risk. Even though imaging studies and laboratory-based tests are accurate at detecting significant steatosis and/or advanced fibrosis, respectively, the diagnosis and characterization of NAFLD ultimately depend on histopathologic evaluation, as the parenchymal alterations that comprise the spectrum of injury in NAFLD include patterns as well as specific lesions. Histologic findings in children may differ from those in adults. In this Review, the histologic features that are diagnostic and discriminatory between steatosis and steatohepatitis, the significance of the distinction between steatosis and steatohepatitis, the types and locations of fibrosis, and the histologic variances between adult and pediatric NAFLD are discussed. Clinical advantages as well as potential drawbacks of liver biopsy are presented. Current pathophysiologic concepts relevant to histologic findings are discussed.
Bernard Zinman - One of the best experts on this subject based on the ideXlab platform.
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elevated c reactive protein in native canadian children an ominous early Complication of childhood Obesity
Diabetes Obesity and Metabolism, 2006Co-Authors: Ravi Retnakaran, Anthony J Hanley, Philip W Connelly, Stewart B Harris, Bernard ZinmanAbstract:Aim: Subclinical inflammation has been proposed as a pathophysiologic mechanism linking Obesity with vascular and metabolic disease. Native North American populations are experiencing high prevalence rates of both (i) childhood Obesity and (ii) adult cardiovascular disease (CVD) and type 2 diabetes. Thus, we sought to determine whether subclinical inflammation is an early Complication of Obesity in Native children. Methods: Serum concentrations of the inflammatory biomarker C-reactive protein (CRP) were assessed in a population-based, cross-sectional study of the Sandy Lake Oji-Cree community of Northern Ontario, Canada, involving 228 children aged 10–19 years (mean age 14.8). Results: Median CRP in this population was 0.5 mg/l (interquartile range 0.18–1.79 mg/l). CRP levels were higher than age-matched reference data from the Third National Health and Nutrition Examination Survey (NHANES III). Importantly, fully 15.8% of the children of this community had CRP concentrations between 3 and 10 mg/l, a range that identifies adults at high risk of CVD. Moreover, increasing CRP concentration in this paediatric population was associated with an enhanced CV risk profile, consisting of increased adiposity, higher insulin resistance, worsening lipid profile (higher total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B and total cholesterol : high-density-lipoprotein cholesterol ratio), increased leptin and decreased adiponectin. On multivariate analysis, waist circumference and interleukin-6 (IL-6) emerged as independent determinants of CRP concentration. Conclusion: Subclinical inflammation is an early Complication of childhood Obesity in Native children and may foreshadow an increased burden of CVD and type 2 diabetes in the future.