scholarly journals Luteolin-Enriched Artichoke Leaf Extract Alleviates the Metabolic Syndrome in Mice with High-Fat Diet-Induced Obesity

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 979 ◽  
Author(s):  
Eun-Young Kwon ◽  
So Kim ◽  
Myung-Sook Choi
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Diet Induced Obesity ◽  
The Metabolic Syndrome

This current study aimed to elucidate the effects and possible underlying mechanisms of long-term supplementation with dietary luteolin (LU)-enriched artichoke leaf (AR) in high-fat diet (HFD)-induced obesity and its complications (e.g., dyslipidemia, insulin resistance, and non-alcoholic fatty liver disease) in C57BL/6N mice. The mice were fed a normal diet, an HFD, or an HFD plus AR or LU for 16 weeks. In the HFD-fed mice, AR decreased the adiposity and dyslipidemia by decreasing lipogenesis while increasing fatty acid oxidation, which contributed to better hepatic steatosis. LU also prevented adiposity and hepatic steatosis by suppressing lipogenesis while increasing biliary sterol excretion. Moreover, AR and LU prevented insulin sensitivity by decreasing the level of plasma gastric inhibitory polypeptide and activity of hepatic glucogenic enzymes, which may be linked to the lowering of inflammation as evidenced by the reduced plasma interleukin (IL)-6, IL-1β, and plasminogen activator inhibitor-1 levels. Although the anti-metabolic syndrome effects of AR and LU were similar, the anti-adiposity and anti-dyslipidemic effects of AR were more pronounced. These results in mice with diet-induced obesity suggest that long-term supplementation with AR can prevent adiposity and related metabolic disorders such as dyslipidemia, hepatic steatosis, insulin resistance, and inflammation.

scholarly journals Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis

2009 ◽  
Vol 297 (6) ◽  
pp. E1420-E1429 ◽  
Author(s):  
Frederic Preitner ◽  
Nimesh Mody ◽  
Timothy E. Graham ◽  
Odile D. Peroni ◽  
Barbara B. Kahn
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Retinol Binding Protein ◽  
Term Therapy ◽  
High Fat ◽  
Diet Induced Obesity

The synthetic retinoid Fenretinide (FEN) increases insulin sensitivity in obese rodents and is in early clinical trials for treatment of insulin resistance in obese humans with hepatic steatosis (46). We aimed to determine the physiological mechanisms for the insulin-sensitizing effects of FEN. Wild-type mice were fed a high-fat diet (HFD) with or without FEN from 4–5 wk to 36–37 wk of age (preventive study) or following 22 wk of HF diet-induced obesity (12 wk intervention study). Retinol-binding protein-4 (RBP4) knockout mice were also fed the HFD with or without FEN in a preventive study. FEN had minimal effects on HFD-induced body weight gain but markedly reduced HFD-induced adiposity and hyperleptinemia in both studies. FEN-HFD mice gained epididymal fat but not subcutaneous or visceral fat mass in contrast to HFD mice without FEN. FEN did not have a measurable effect on energy expenditure, food intake, physical activity, or stool lipid content. Glucose infusion rate during hyperinsulinemic-euglycemic clamp was reduced 86% in HFD mice compared with controls and was improved 3.6-fold in FEN-HFD compared with HFD mice. FEN improved insulin action on glucose uptake and glycogen levels in muscle, insulin-stimulated suppression of hepatic glucose production, and suppression of serum FFA levels in HFD mice. Remarkably, FEN also reduced hepatic steatosis. In RBP4 knockout mice, FEN reduced the HFD-induced increase in adiposity and hyperleptinemia. In conclusion, long-term therapy with FEN partially prevents or reverses obesity, insulin resistance, and hepatic steatosis in mice on HFD. The anti-adiposity effects are independent of the RBP4 lowering effect.

Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

2021 ◽  
Author(s):  
Haizhao Song ◽  
Xinchun Shen ◽  
Yang Zhou ◽  
Xiaodong Zheng
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Obese Mice ◽  
Black Rice ◽  
High Fat ◽  
Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

scholarly journals Fetal origins of insulin resistance and obesity

2005 ◽  
Vol 64 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Claire J. Stocker ◽  
Jonathan R. S. Arch ◽  
Michael A. Cawthorne
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
G Protein ◽  
High Fat Diet ◽  
High Fat ◽  
Fetal Origins ◽  
Thrifty Phenotype ◽  
The Metabolic Syndrome ◽  
Increased Susceptibility

A number of epidemiological studies worldwide have demonstrated a relationship between poor early growth and an increased susceptibility to insulin resistance, visceral obesity, type 2 diabetes and other features of the metabolic syndrome in adulthood. However, the mechanistic basis of this relationship and the relative roles of genes and the environment remain a subject of debate. The ‘thrifty phenotype’ hypothesis proposes that poor fetal nutrition leads to programming of metabolism and an adult phenotype that is adapted to poor but not plentiful nutrition. The maternal reduced-protein rat model has been used to examine the importance of the maternal environment in determining susceptibility to adult disease. Pregnant and lactating rat dams are fed a diet containing 80 g protein/kg as compared with 200 g protein/kg, which leads to growth restriction in utero. Offspring of low-protein dams have increased susceptibility to diabetes, insulin resistance and hypertension when fed a palatable high-fat diet that promotes obesity. Administration of leptin during pregnancy and lactation to these protein-restricted dams produces offspring that have increased metabolic rate and do not become obese or insulin resistant when fed on a high-fat diet. Increased glucocorticoid exposure, particularly during late gestation, has been linked with insulin resistance in adulthood. High levels of fetal glucocorticoids may result from a decreased activity of placental 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2, which normally protects the fetus from high maternal glucocorticoid levels. Leptin administration to protein-restricted dams inhibits the suppression of 11β-HSD-2 and may be one mechanism by which the metabolic syndrome is prevented.

Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet

2010 ◽  
Vol 119 (6) ◽  
pp. 239-250 ◽  
Author(s):  
Vanessa Souza-Mello ◽  
Bianca M. Gregório ◽  
Fernando S. Cardoso-de-Lemos ◽  
Laís de Carvalho ◽  
Márcia B. Aguila ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Oral Glucose ◽  
Free Access ◽  
High Fat ◽  
The Metabolic Syndrome ◽  
Glucose Transporter 2 ◽  
Drug Treatments

The aim of the present study was to evaluate the effects of monotherapies and combinations of drugs on insulin sensitivity, adipose tissue morphology, and pancreatic and hepatic remodelling in C57BL/6 mice fed on a very HF (high-fat) diet. Male C57BL/6 mice were fed on an HF (60% lipids) diet or SC (standard chow; 10% lipids) diet for 10 weeks, after which time the following drug treatments began: HF-T (HF diet treated with telmisartan; 5.2 mg·kg−1 of body weight·day−1), HF-S (HF diet treated with sitagliptin; 1.08 g·kg−1 of body weight·day−1), HF-M (HF diet treated with metformin; 310.0 mg·kg−1 of body weight·day−1), HF-TM (HF diet treated with telmisartan+metformin), HF-TS (HF diet treated with telmisartan+sitagliptin) and HF-SM (HF diet treated with sitagliptin+metformin). Treated groups also had free access to the HF diet, and treatments lasted for 6 weeks. Morphometry, stereological tools, immunostaining, ELISA, Western blot analysis and electron microscopy were used. The HF diet yielded an overweight phenotype, an increase in oral glucose intolerance, hyperinsulinaemia, hypertrophied islets and adipocytes, stage 2 steatosis (>33%), and reduced liver PPAR-α (peroxisome-proliferator-activated receptor-α) and GLUT-2 (glucose transporter-2) levels, concomitant with enhanced SREBP-1 (sterol-regulatory-element-binding protein-1) expression (P<0.0001). Conversely, all drug treatments resulted in significant weight loss, a reversal of insulin resistance, islet and adipocyte hypertrophy, and alleviated hepatic steatosis. Only the HF-T and HF-TS groups had body weights similar to the SC group at the end of the experiment, and the latter treatment reversed hepatic steatosis. Increased PPAR-α immunostaining in parallel with higher GLUT-2 and reduced SREBP-1 expression may explain the favourable hepatic outcomes. Restoration of adipocyte size was consistent with higher adiponectin levels and lower TNF-α (tumour necrosis factor-α) levels (P<0.0001) in the drug-treated groups. In conclusion, all of the drug treatments were effective in controlling the metabolic syndrome. The best results were achieved using telmisartan and sitagliptin as monotherapies or as a dual treatment, combining partial PPAR-γ agonism and PPAR-α activation in the liver with extended incretin action.

scholarly journals Deepure Tea Improves High Fat Diet-Induced Insulin Resistance and Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jing-Na Deng ◽  
Juan Li ◽  
Hong-Na Mu ◽  
Yu-Ying Liu ◽  
Ming-Xia Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthesis ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
High Fat ◽  
The Metabolic Syndrome

This study was to explore the protective effects of Deepure tea against insulin resistance and hepatic steatosis and elucidate the potential underlying molecular mechanisms. C57BL/6 mice were fed with a high fat diet (HFD) for 8 weeks to induce the metabolic syndrome. In the Deepure tea group, HFD mice were administrated with Deepure tea at 160 mg/kg/day by gavage for 14 days. The mice in HFD group received water in the same way over the same period. The age-matched C57BL/6 mice fed with standard chow were used as normal control. Compared to the mice in HFD group, mice that received Deepure tea showed significantly reduced plasma insulin and improved insulin sensitivity. Deepure tea increased the expression of insulin receptor substrate 2 (IRS-2), which plays an important role in hepatic insulin signaling pathway. Deepure tea also led to a decrease in hepatic fatty acid synthesis and lipid accumulation, which were mediated by the downregulation of sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthesis (FAS), and acetyl-CoA carboxylase (ACC) proteins that are involved in liver lipogenesis. These results suggest that Deepure tea may be effective for protecting against insulin resistance and hepatic steatosis via modulating IRS-2 and downstream signaling SREBP-1c, FAS, and ACC.

scholarly journals P2Y2R Deficiency Ameliorates Hepatic Steatosis by Reducing Lipogenesis and Enhancing Fatty Acid β-Oxidation through AMPK and PGC-1α Induction in High-Fat Diet-Fed Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 5528
Author(s):  
Theodomir Dusabimana ◽  
Eun Jung Park ◽  
Jihyun Je ◽  
Kyuho Jeong ◽  
Seung Pil Yun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Purinergic Receptor ◽  
Lipolytic Enzyme ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Mitochondrial Fatty Acid

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease associated with obesity and insulin resistance. Activation of the purinergic receptor P2Y2R has been reported to promote adipogenesis, inflammation and dyslipidemia in adipose tissues in obese mice. However, the role of P2Y2R and its mechanisms in NAFLD remain unknown. We hypothesized that P2Y2R deficiency may play a protective role in NAFLD by modulating lipid metabolism in the liver. In this study, we fed wild type and P2Y2R knockout mice with a high-fat diet (HFD) for 12 weeks and analyzed metabolic phenotypes. First, P2Y2R deficiency effectively improved insulin resistance with a reduction in body weight and plasma insulin. Second, P2Y2R deficiency attenuated hepatic lipid accumulation and injury with reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Third, P2Y2R deficiency decreased the expression of fatty acid synthesis mediators (cluster of differentiation (CD36), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1)); and increased the expression of adipose triglyceride lipase (ATGL), a lipolytic enzyme. Mechanistically, P2Y2R deficiency increased the AMP-activated protein kinase (AMPK) activity to improve mitochondrial fatty acid β-oxidation (FAO) by regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1A (CPT1A)-mediated FAO pathway. In addition, P2Y2R deficiency increased peroxisome proliferator-activated gamma co-activator-1α (PGC-1α)-mediated mitochondrial biogenesis. Conclusively, P2Y2R deficiency ameliorated HFD-induced hepatic steatosis by enhancing FAO through AMPK signaling and PGC-1α pathway, suggesting P2Y2R as a promising therapeutic target for NAFLD.

scholarly journals Long-Term Dietary Nitrate Supplementation Does Not Prevent Development of the Metabolic Syndrome in Mice Fed a High-Fat Diet

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
V. B. Matthews ◽  
R. Hollingshead ◽  
H. Koch ◽  
K. D. Croft ◽  
N. C. Ward
Keyword(s):  
Metabolic Syndrome ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
High Fat ◽  
Running Wheel ◽  
Dietary Nitrate ◽  
The Metabolic Syndrome ◽  
Normal Chow ◽  
Nitrate Supplementation

Background. Nitric oxide (NO) is an important vascular signaling molecule that plays a role in vascular homeostasis. A reduction in NO bioavailability is thought to contribute to endothelial dysfunction, an early risk factor for both cardiovascular disease and type 2 diabetes. Dietary nitrate, through the nitrate-nitrite-NO pathway, may provide an alternate source of NO when the endogenous eNOS system is compromised. In addition to a role in the vascular system, NO may also play a role in the metabolic syndrome including obesity and glucose tolerance. Aim. To investigate the effect of long-term dietary nitrate supplementation on development of the metabolic syndrome in mice fed a high-fat diet. Methods. Following 1 week of acclimatisation, male (6–8 weeks) C57BL6 mice were randomly assigned to the following groups (10/group) for 12 weeks: (i) normal chow + NaCl (1 mmol/kg/day), (ii) normal chow + NaNO3 (1 mmol/kg/day), (iii) high-fat diet + NaCl (1 mmol/kg/day), and (iv) high-fat diet + NaNO3 (1 mmol/kg/day). Body weight and food consumption were monitored weekly. A subset of mice (5/group) underwent running wheel assessment. At the end of the treatment period, all mice underwent fasting glucose tolerance testing. Caecum contents, serum, and tissues (liver, skeletal muscle, white and brown adipose, and kidney) were collected, frozen, and stored at −80°C until analysis. Results. Consumption of the high-fat diet resulted in significantly greater weight gain that was not affected by dietary nitrate. Mice on the high-fat diet also had impaired glucose tolerance that was not affected by dietary nitrate. There was no difference in adipose tissue expression of thermogenic proteins or energy expenditure as assessed by the running wheel activity. Mice on the high-fat diet and those receiving dietary nitrate had reduced caecum concentrations of both butyrate and propionate. Conclusions. Dietary nitrate does not prevent development of the metabolic syndrome in mice fed a high-fat diet. This may be due, in part due, to reductions in the concentration of important short-chain fatty acids.

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