Sex-dependent differences in rat hepatic lipid accumulation and insulin sensitivity in response to diet-induced obesity

2012 ◽  
Vol 90 (2) ◽  
pp. 164-172 ◽  
Author(s):  
Antònia Nadal-Casellas ◽  
Ana Maria Proenza ◽  
Isabel Lladó ◽  
Magdalena Gianotti
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Insulin Signaling ◽  
Lipid Accumulation ◽  
Dietary Treatment ◽  
Pyruvate Dehydrogenase Kinase ◽  
Female Rats ◽  
Liver Fat ◽  
Standard Diet ◽  
Fat Accumulation

Ectopic deposition of lipids in liver and other extrahepatic tissues alters their function and occurs once adipose tissue fat storage capacity is exceeded. We investigated sexual dimorphism in the effects of dietary obesity on the liver insulin signaling pathway, as well as its connection to differences in hepatic fat accumulation. Ten-week-old Wistar rats of both sexes were fed a standard diet or a high-fat diet for 26 weeks. Insulin, adipokine levels, and glucose tolerance were measured. Lipid content, PPARα mRNA expression and protein levels of insulin receptor subunit β (IRβ), IR substrate 2 (IRS-2), Ser/Thr kinase A (Akt), and pyruvate dehydrogenase kinase isozyme 4 (PDK4) were measured in liver. In control rats, serum parameters and hepatic levels of IRβ, IRS-2, and Akt proteins pointed to a profile of better insulin sensitivity in females. In response to dietary treatment, female rats exhibited a greater increase in body mass and adiposity and lower liver fat accumulation than males, but maintained better glucose tolerance. The reduced insulin signaling capacity in the liver of obese female rats seems to prevent lipid accumulation and probably lipotoxicity-associated hepatic disorders.

scholarly journals Effects of Exercise Training on Molecular Markers of Lipogenesis and Lipid Partitioning in Fructose-Induced Liver Fat Accumulation

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Siham Yasari ◽  
Denis Prud'homme ◽  
Frédérique Tesson ◽  
Marek Jankowski ◽  
Jolanta Gutkowska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Exercise Training ◽  
Unsaturated Fatty Acids ◽  
Regulatory Element ◽  
Female Rats ◽  
Liver Fat ◽  
Standard Diet ◽  
Fat Accumulation ◽  
High Fructose ◽  
The Impact

The present study was designed to investigate the impact of exercise training on lipogenic gene expression in liver and lipid partitioning following the ingestion of a high fructose load. Female rats were exercise-trained for 8 wk or kept sedentary before being submitted to a fasting/refeeding protocol. Rats were further subdivided as follow: rats were fasted for 24 h, refed a standard diet for 24 h, starved for another 24 h, and refed with a standard or a high-fructose diet 24 h before sacrifice. Fructose refeeding was associated with an increase in hepatic lipid content, endocannabinoid receptor 1, sterol regulatory element-binding protein1c, and stearoyl-CoA desaturase1 gene expression in both Sed and TR rats. However, desaturation indexes measured in liver (C16 : 1/C16 : 0 and C18 : 1/C18 : 0) and plasma (C18 : 1/C18 : 0) were higher (P<0.01) in TR than in Sed rats following fructose refeeding. It is concluded that exercise training does not significantly affect fat accumulation and the molecular expression of genes involved in lipogenesis after fasting and fructose refeeding but does modify the partitioning of lipids so as to provide more unsaturated fatty acids in liver without affecting liver fat content.

A combination of borage seed oil and quercetin reduces fat accumulation and improves insulin sensitivity in obese rats

2020 ◽  
Vol 11 (5) ◽  
pp. 4512-4524 ◽  
Author(s):  
Paula Aranaz ◽  
María Zabala ◽  
Ana Romo-Hualde ◽  
David Navarro-Herrera ◽  
Miguel López-Yoldi ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Seed Oil ◽  
Liver Steatosis ◽  
Key Factors ◽  
Fat Accumulation ◽  
Obese Rats

Borage seed oil (BSO) combined with quercetin improves glucose tolerance, insulin sensitivity, liver steatosis and adiposity in pre-obese rats. The combination also inhibits adipogenesis in vitro by affecting some adipogenesis-key factors.

scholarly journals Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome

2011 ◽  
Vol 107 (10) ◽  
pp. 1429-1434 ◽  
Author(s):  
Jinjin Chen ◽  
Ren Wang ◽  
Xiao-Fang Li ◽  
Rui-Liang Wang
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Visceral Fat ◽  
The Other ◽  
Standard Diet ◽  
Fat Pad ◽  
Bifidobacterium Adolescentis ◽  
Fat Accumulation ◽  
Visceral Fat Accumulation ◽  
The Metabolic Syndrome

The aim of the present study was to investigate the effects of Bifidobacterium adolescentis (Bif) supplementation on visceral fat accumulation and insulin sensitivity of the metabolic syndrome in HF-diet-fed rats. Adult male Wistar rats (n 10 per group) were fed four different experimental diets for 12 weeks as follows: standard diet; high-fat (HF) diet; a mix of HF diet and Bif; a mix of standard diet and Bif. Liver, mesenteric fat, epididymal fat, retroperitoneal fat, and inguinal fat, pancreas and triceps surae in all four groups of the rats were weighed, while liver steatosis and insulin sensitivity were evaluated at the end point of the study. As the number of intestinal Bifidobacterium species decreased obviously, fat pad weight and body weight increased significantly in the HF group compared with in the other three groups (P <0·05). Addition of Bif led to a reduction in body weight and fat pad weight (P <0·05). With an increase in liver weight, more severe steatosis of hepatocytes was observed in the HF group compared with in the other three groups. A significant decrease of the glucose infusion rate and pancreas weight was found in the HF group (P <0·05). This deleterious effect was alleviated when Bif was added to the diets. Bifidobacterium supplementation ameliorated visceral fat accumulation and insulin sensitivity of the metabolic syndrome in HF-diet-fed rats.

scholarly journals Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

2011 ◽  
Vol 47 (2) ◽  
pp. 129-143 ◽  
Author(s):  
Carolina Gustavsson ◽  
Tomoyoshi Soga ◽  
Erik Wahlström ◽  
Mattias Vesterlund ◽  
Alireza Azimi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Stress Responses ◽  
Female Rats ◽  
Male Rats ◽  
High Fat ◽  
Prediabetic State ◽  
Flight Mass Spectrometry ◽  
Zucker Diabetic Fatty Rats

Male Zucker diabetic fatty (mZDF) rats spontaneously develop type 2 diabetes, whereas females only become diabetic when fed a diabetogenic high-fat diet (high-fat-fed female ZDF rat, HF-fZDF). The aim of this study was to investigate if differences in liver functions could provide clues to this sex difference. Non-diabetic obese fZDF rats were compared with either mZDF or HF-fZDF regarding hepatic molecular profiles, to single out those components that might be protective in the females. High-fat feeding in fZDF led to enhanced weight gain, increased blood glucose and insulin levels, reduced insulin sensitivity and a trend towards reduced glucose tolerance, indicative of a prediabetic state. mZDF rats were diabetic, with low levels of insulin, high levels of glucose, reduced insulin sensitivity and impaired glucose tolerance. Transcript profiling and capillary electrophoresis time-of-flight mass spectrometry were used to indentify hepatic transcripts and metabolites that might be related to this. Many diet-induced alterations in transcript and metabolite levels in female rats were towards a ‘male-like’ phenotype, including reduced lipogenesis, increased fatty acid (FA) oxidation and increased oxidative stress responses. Alterations detected at the level of hepatic metabolites, indicated lower capacity for glutathione (GSH) production in male rats, and higher GSH turnover in females. Taken together, this could be interpreted as if anabolic pathways involving lipogenesis and lipid output might limit the degree of FA oxidation and oxidative stress in female rats. Together with a greater capacity to produce GSH, these hepatic sex differences might contribute to the sex-different development of diabetes in ZDF rats.

scholarly journals Hepatic fat and glucose tolerance in women with recent gestational diabetes

2018 ◽  
Vol 6 (1) ◽  
pp. e000549 ◽  
Author(s):  
Sadia Mehmood ◽  
Myles Margolis ◽  
Chang Ye ◽  
Louise Maple-Brown ◽  
Anthony J Hanley ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Post Partum ◽  
Tolerance Test ◽  
Liver Fat ◽  
Oral Glucose ◽  
Increased Risk ◽  
Hepatic Fat

ObjectiveWomen with a history of gestational diabetes mellitus (GDM) have an elevated risk of ultimately developing pre-diabetes and diabetes later in life. They also have an increased prevalence of fatty liver, but recent studies have reported conflicting findings on whether hepatic fat affects their risk of pre-diabetes/diabetes. Thus, we sought to evaluate the associations of liver fat with glucose homeostasis and determinants thereof in women with and without recent gestational dysglycemia.MethodsTwo hundred and fifty-seven women underwent an antepartum oral glucose tolerance test (OGTT), which diagnosed 97 with GDM, 40 with gestational impaired glucose tolerance (GIGT), and 120 with normal glucose tolerance (NGT). At a mean of 4.8 years post partum, they underwent an OGTT (which revealed that 52 had progressed to pre-diabetes/diabetes) and hepatic ultrasound, on which liver fat was graded as none (n=164), mild (n=66), or moderate (n=27).ResultsLiver fat was more prevalent in women with previous GDM than in those with GIGT or NGT (p=0.009) and in women with current pre-diabetes/diabetes than in those without (p=0.0003). As the severity of liver fat increased, there was a progressive worsening of insulin sensitivity and beta-cell function, coupled with rising fasting and 2-hour glucose (all p<0.0001). On multiple linear regression analyses, moderate liver fat was independently associated with lower insulin sensitivity (p=0.0002) and higher 2-hour glucose (p=0.009). Moreover, moderate liver fat emerged as an independent predictor of pre-diabetes/diabetes (OR=3.66, 95% CI 1.1 to 12.5).ConclusionThe higher prevalence of liver fat in women with previous GDM is associated with their increased risk of pre-diabetes/diabetes.

scholarly journals Adipose Triglyceride Lipase-Null Mice Are Resistant to High-Fat Diet–Induced Insulin Resistance Despite Reduced Energy Expenditure and Ectopic Lipid Accumulation

Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 48-58 ◽  
Author(s):  
Andrew J. Hoy ◽  
Clinton R. Bruce ◽  
Sarah M. Turpin ◽  
Alexander J. Morris ◽  
Mark A. Febbraio ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Glucose Tolerance ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Adipose Triglyceride Lipase ◽  
Wild Type ◽  
High Fat

Abstract Adipose triglyceride lipase (ATGL) null (−/−) mice store vast amounts of triacylglycerol in key glucoregulatory tissues yet exhibit enhanced insulin sensitivity and glucose tolerance. The mechanisms underpinning these divergent observations are unknown but may relate to the reduced availability of circulating fatty acids. The aim of this study was to determine whether the enhancements in insulin stimulated glucose metabolism in ATGL−/− mice persist when challenged with a high-fat diet. ATGL−/− mice fed a low-fat diet exhibit improved whole-body insulin sensitivity and glucose tolerance compared with wild-type mice. Wild-type mice became hyperlipidemic and insulin-resistant when challenged with a high-fat diet (HFD, 60% fat) for 4 wk. ATGL−/− mice fed a HFD had elevated circulating fatty acids but had reduced fasting glycemia compared to pre–high-fat diet levels and were refractory to glucose intolerance and insulin resistance. This protection from high-fat diet–induced metabolic perturbations was associated with a preference for fatty acid utilization but reduced energy expenditure and no change in markers of mitochondrial capacity or density. The protection from high-fat diet–induced insulin resistance in ATGL−/− mice was due to increased cardiac and liver insulin-stimulated glucose clearance despite increased lipid content in these tissues. Additionally, there was no difference in skeletal muscle insulin-stimulated glucose disposal, but there was a reduction observed in brown adipose tissue. Overall, these results show that ATGL−/− mice are protected from HFD-induced insulin resistance and reveal a tissue specific disparity between lipid accumulation and insulin sensitivity.

scholarly journals β-Hydroxybutyrate is reduced in humans with obesity-related NAFLD and displays a dose-dependent effect on skeletal muscle mitochondrial respiration in vitro

2020 ◽  
Vol 319 (1) ◽  
pp. E187-E195 ◽  
Author(s):  
Jacob T. Mey ◽  
Melissa L. Erickson ◽  
Christopher L. Axelrod ◽  
William T. King ◽  
Chris A. Flask ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Insulin Sensitivity ◽  
Mitochondrial Respiration ◽  
Liver Fat ◽  
Whole Body ◽  
Fat Accumulation ◽  
Impaired Insulin ◽  
Hepatic Fat

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation and impaired insulin sensitivity. Reduced hepatic ketogenesis may promote these pathologies, but data are inconclusive in humans and the link between NAFLD and reduced insulin sensitivity remains obscure. We investigated individuals with obesity-related NAFLD and hypothesized that β-hydroxybutyrate (βOHB; the predominant ketone species) would be reduced and related to hepatic fat accumulation and insulin sensitivity. Furthermore, we hypothesized that ketones would impact skeletal muscle mitochondrial respiration in vitro. Hepatic fat was assessed by 1H-MRS in 22 participants in a parallel design, case control study [Control: n = 7, age 50 ± 6 yr, body mass index (BMI) 30 ± 1 kg/m2; NAFLD: n = 15, age 57 ± 3 yr, BMI 35 ± 1 kg/m2]. Plasma assessments were conducted in the fasted state. Whole body insulin sensitivity was determined by the gold-standard hyperinsulinemic-euglycemic clamp. The effect of ketone dose (0.5–5.0 mM) on mitochondrial respiration was conducted in human skeletal muscle cell culture. Fasting βOHB, a surrogate measure of hepatic ketogenesis, was reduced in NAFLD (−15.6%, P < 0.01) and correlated negatively with liver fat ( r2 = 0.21, P = 0.03) and positively with insulin sensitivity ( r2 = 0.30, P = 0.01). Skeletal muscle mitochondrial oxygen consumption increased with low-dose ketones, attributable to increases in basal respiration (135%, P < 0.05) and ATP-linked oxygen consumption (136%, P < 0.05). NAFLD pathophysiology includes impaired hepatic ketogenesis, which is associated with hepatic fat accumulation and impaired insulin sensitivity. This reduced capacity to produce ketones may be a potential link between NAFLD and NAFLD-associated reductions in whole body insulin sensitivity, whereby ketone concentrations impact skeletal muscle mitochondrial respiration.

scholarly journals Anacardic acid mitigates liver fat accumulation and impaired glucose tolerance in mice fed a high‐fat and high‐sucrose diet

2020 ◽  
Vol 8 (2) ◽  
pp. 796-804 ◽  
Author(s):  
Sangwon Chung ◽  
Eun Ju Shin ◽  
Hyo‐Kyoung Choi ◽  
Jae Ho Park ◽  
Jin‐Taek Hwang
Keyword(s):  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Anacardic Acid ◽  
Liver Fat ◽  
High Fat ◽  
Fat Accumulation ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

Coffee polyphenols suppress diet-induced body fat accumulation by downregulating SREBP-1c and related molecules in C57BL/6J mice

2011 ◽  
Vol 300 (1) ◽  
pp. E122-E133 ◽  
Author(s):  
Takatoshi Murase ◽  
Koichi Misawa ◽  
Yoshihiko Minegishi ◽  
Masafumi Aoki ◽  
Hideo Ominami ◽  
...  
Keyword(s):  
Body Fat ◽  
High Fat Diet ◽  
Active Form ◽  
Pyruvate Dehydrogenase Kinase ◽  
Liver Fat ◽  
Mrna Levels ◽  
Acetyl Coa Carboxylase ◽  
High Fat ◽  
Acetyl Coa ◽  
Fat Accumulation

The prevalence of obesity is increasing globally, and obesity is a major risk factor for type 2 diabetes and cardiovascular disease. We investigated the effects of coffee polyphenols (CPP), which are abundant in coffee and consumed worldwide, on diet-induced body fat accumulation. C57BL/6J mice were fed either a control diet, a high-fat diet, or a high-fat diet supplemented with 0.5 to 1.0% CPP for 2–15 wk. Supplementation with CPP significantly reduced body weight gain, abdominal and liver fat accumulation, and infiltration of macrophages into adipose tissues. Energy expenditure evaluated by indirect calorimetry was significantly increased in CPP-fed mice. The mRNA levels of sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase-1 and -2, stearoyl-CoA desaturase-1, and pyruvate dehydrogenase kinase-4 in the liver were significantly lower in CPP-fed mice than in high-fat control mice. Similarly, CPP suppressed the expression of these molecules in Hepa 1–6 cells, concomitant with an increase in microRNA-122. Structure-activity relationship studies of nine quinic acid derivatives isolated from CPP in Hepa 1–6 cells suggested that mono- or di-caffeoyl quinic acids (CQA) are active substances in the beneficial effects of CPP. Furthermore, CPP and 5-CQA decreased the nuclear active form of SREBP-1, acetyl-CoA carboxylase activity, and cellular malonyl-CoA levels. These findings indicate that CPP enhances energy metabolism and reduces lipogenesis by downregulating SREBP-1c and related molecules, which leads to the suppression of body fat accumulation.

scholarly journals Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins

2016 ◽  
pp. jc.2015-3512 ◽  
Author(s):  
Joel T. Rämö ◽  
Sanna M. Kaye ◽  
Sakari Jukarainen ◽  
Leonie H. Bogl ◽  
Antti Hakkarainen ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Young Adult ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Liver Fat ◽  
Metabolite Profiles ◽  
Adult Twins
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