scholarly journals Cardioprotective Effects of Metformin and Vildagliptin in Adult Rats with Insulin Resistance Induced by a High-Fat Diet

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3878-3885 ◽  
Author(s):  
Nattayaporn Apaijai ◽  
Hiranya Pintana ◽  
Siriporn C. Chattipakorn ◽  
Nipon Chattipakorn
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Body Weight ◽  
Mitochondrial Dysfunction ◽  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
High Fat ◽  
Antidiabetic Drug ◽  
Sympathovagal Imbalance

Insulin resistance has been shown to be associated with cardiac sympathovagal imbalance, myocardial dysfunction, and cardiac mitochondrial dysfunction. Whereas metformin is a widely used antidiabetic drug to improve insulin resistance, vildagliptin is a novel oral antidiabetic drug in a group of dipeptidyl peptidase-4 inhibitors in which its cardiac effect is unclear. This study aimed to determine the cardiovascular effects of metformin and vildagliptin in rats with insulin resistance induced by high-fat diet. Male Wistar rats were fed with either a normal diet or high-fat diet (n =24 each) for 12 wk. Rats in each group were divided into three subgroups to receive the vehicle, metformin (30 mg/kg, twice daily), or vildagliptin (3 mg/kg, once daily) for another 21 d. Heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined and compared among these treatment groups. Rats exposed to a high-fat diet developed increased body weight, visceral fat, plasma insulin, cholesterol, oxidative stress, depressed HRV, and cardiac mitochondrial dysfunction. Metformin and vildagliptin did not alter body weight and plasma glucose levels but decreased the plasma insulin, total cholesterol, and oxidative stress levels. Although both metformin and vildagliptin attenuated the depressed HRV, cardiac dysfunction, and cardiac mitochondrial dysfunction, vildagliptin was more effective in this prevention. Furthermore, only vildagliptin prevented cardiac mitochondrial membrane depolarization caused by consumption of a high-fat diet. We concluded that vildagliptin is more effective in preventing cardiac sympathovagal imbalance and cardiac dysfunction, as well as cardiac mitochondrial dysfunction, than metformin in rats with insulin resistance induced by high-fat diet.

scholarly journals Comparative effects of sex hormone deprivation on the brain of insulin-resistant rats

2019 ◽  
Vol 241 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Jirapas Sripetchwandee ◽  
Hiranya Pintana ◽  
Piangkwan Sa-nguanmoo ◽  
Chiraphat Boonnag ◽  
Wasana Pratchayasakul ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Cognitive Decline ◽  
Mitochondrial Dysfunction ◽  
Dendritic Spine ◽  
High Fat Diet ◽  
High Fat ◽  
Long Term Depression ◽  
Impaired Insulin

Obese-insulin resistance following chronic high-fat diet consumption led to cognitive decline through several mechanisms. Moreover, sex hormone deprivation, including estrogen and testosterone, could be a causative factor in inducing cognitive decline. However, comparative studies on the effects of hormone deprivation on the brain are still lacking. Adult Wistar rats from both genders were operated upon (sham operations or orchiectomies/ovariectomies) and given a normal diet or high-fat diet for 4, 8 and 12 weeks. Blood was collected to determine the metabolic parameters. At the end of the experiments, rats were decapitated and their brains were collected to determine brain mitochondrial function, brain oxidative stress, hippocampal plasticity, insulin-induced long-term depression, dendritic spine density and cognition. We found that male and female rats fed a high-fat diet developed obese-insulin resistance by week 8 and brain defects via elevated brain oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity, reduced dendritic spine density and cognitive decline by week 12. In normal diet-fed rats, estrogen deprivation, not testosterone deprivation, induced obese-insulin resistance, oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity and reduced dendritic spine density. In high-fat–diet-fed rats, estrogen deprivation, not testosterone deprivation, accelerated and aggravated obese-insulin resistance and brain defects at week 8. In conclusion, estrogen deprivation aggravates brain dysfunction more than testosterone deprivation through increased oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression and dendritic spine reduction. These findings may explain clinical reports which show more severe cognitive decline in aging females than males with obese-insulin resistance.

scholarly journals Moringa oleifera leaf extract ameliorated high-fat diet-induced obesity, oxidative stress and disrupted metabolic hormones

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Azza I. Othman ◽  
Maher A. Amer ◽  
Asmaa S. Basos ◽  
Mohammed A. El-Missiry
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Body Weight ◽  
Liver Function ◽  
High Fat Diet ◽  
Leaf Extract ◽  
Moringa Oleifera ◽  
High Fat ◽  
Metabolic Hormones ◽  
Lipid Fractions

Abstract Background Obesity is a health problem in many countries, and maintaining a perfect weight is challenging. Moringa oleifera leaf extract (ME) is rich in polyphenols with antioxidant and pharmaceutical potential. The present study investigated the potential protective effect of Moringa oleifera leaf extract against obesity induced from a high-fat diet (HFD), oxidative stress and disruption of metabolic hormones compared to simvastatin (SIM) or their combination. Results Rats fed a HFD for 6 weeks exhibited a significant increase in body weight and levels of serum glucose and lipid fractions, verifying an obesity state. There were also higher levels of insulin and leptin and lower gherlin in sera of HFD rats compared to the levels in control rats. Homeostasis model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and the atherogenic index were elevated, indicating the development of insulin resistance and dyslipidaemia in these rats. These changes were accompanied with a significant increase in oxidative stress, as indicated by elevated lipid peroxidation and protein oxidation with low levels of antioxidants in liver. The activities of liver function enzymes, including aspartate amino transferase, alanine amino transferase, alkaline phosphatase and gamma glutamyltransferase, were also significantly increased in serum. Concurrent treatment with 300 mg/kg ME for 6 weeks ameliorated the increase in body weight and improved the levels of glucose, lipid fractions and metabolic hormones, indicating the anti-obesity effect and amelioration of tissue insulin resistance potential of ME. ME treatment also normalized oxidative stress and antioxidants in liver and improved liver function enzymes, indicating the antioxidant potential of ME. The effects of ME were similar to SIM, and the combination of these agents was better than each agent alone. Conclusion We propose that ME extract has anti-obesity and antioxidant potential and may be used as a lipid-lowering drug to control weight, obesity and its pathophysiological consequences.

scholarly journals Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet

2010 ◽  
Vol 299 (4) ◽  
pp. R1082-R1090 ◽  
Author(s):  
Jill K. Morris ◽  
Gregory L. Bomhoff ◽  
John A. Stanford ◽  
Paige C. Geiger
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Locomotor Activity ◽  
Substantia Nigra ◽  
High Fat Diet ◽  
Model Assessment ◽  
High Fat

Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.

scholarly journals Regulation of plasma leptin in mice: influence of age, high-fat diet, and fasting

1997 ◽  
Vol 273 (1) ◽  
pp. R113-R120 ◽  
Author(s):  
B. Ahren ◽  
S. Mansson ◽  
R. L. Gingerich ◽  
P. J. Havel
Keyword(s):  
Body Weight ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Age Groups ◽  
Fat Content ◽  
High Fat ◽  
Background Strain ◽  
Plasma Leptin

Mechanisms regulating circulating leptin are incompletely understood. We developed a radioimmunoassay for mouse leptin to examine the influence of age, dietary fat content, and fasting on plasma concentrations of leptin in the background strain for the ob/ob mouse, the C57BL/6J mouse. Plasma leptin increased with age [5.3 +/- 0.6 ng/ml at 2 mo (n = 23) vs. 14.2 +/- 1.6 ng/ml at 11 mo (n = 15), P < 0.001]. Across all age groups (2-11 mo, n = 160), log plasma leptin correlated with body weight (r = 0.68, P < 0.0001), plasma insulin (r = 0.38, P < 0.001), and amount of intra-abdominal fat (r = 0.90, P < 0.001), as revealed by magnetic resonance imaging. Plasma leptin was increased by a high-fat diet (58% fat for 10 mo) and reduced by fasting for 48 h. The reduction of plasma leptin was correlated with the reduction of plasma insulin (r = 0.43, P = 0.012) but not with the initial body weight or the change in body weight. Moreover, the reduction in plasma leptin by fasting was impaired by high-fat diet. Thus plasma leptin in C57BL/6J mice 1) increases with age or a high-fat diet; 2) correlates with body weight, fat content, and plasma insulin; and 3) is reduced during fasting by an action inhibited by high-fat diet and related to changes of plasma insulin.

Triterpenoid-Rich Fraction from Ilex hainanensis Merr. Attenuates Non-Alcoholic Fatty Liver Disease Induced by High Fat Diet in Rats

2013 ◽  
Vol 41 (03) ◽  
pp. 487-502 ◽  
Author(s):  
Wei-Xi Cui ◽  
Jie Yang ◽  
Xiao-Qing Chen ◽  
Qian Mao ◽  
Xiang-Lan Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Density Lipoprotein ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Cyp2e1 Expression ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) has become a major challenge to the healthcare system. This study was designed to evaluate the effect of the triterpenoid-rich fraction (TF) from Ilex hainanensis Merr. on NAFLD. Male Sprague-Dawley (SD) rats were fed a normal diet (control) or high fat diet (NAFLD model). After four weeks, the high fat diet group was orally administrated TF (250 mg/kg) for another two weeks. High fat diet fed rats displayed hyperlipidemia and a decline in liver function compared with control. However, administration with TF could effectively improve these symptoms, as demonstrated by decreasing the plasma levels of triglyceride (p <0.05), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.05), alanine transaminase (p < 0.05), aspartate aminotransferase (p < 0.01), liver index (p < 0.05) and insulin resistance index (p < 0.05) while increasing the high-density lipoprotein cholesterol (p < 0.05). Meanwhile, histopathological examination of livers also showed that TF could reduce the incidence of liver lesions induced by high fat diet. Furthermore, TF could alleviate oxidative stress and inflammation status indicated by the decline malondialdehyde and superoxide dismutase levels (p < 0.01, both) and levels of interleukin 6 and tumor necrosis factor-α (p < 0.05). In addition, immunohistochemistry showed TF evidently elevated the peroxisome proliferator-activated receptor (PPARα) expression (p < 0.01), while it diminished the Cytochrome P450 2E1 (CYP2E1) expression (p < 0.01) in liver. These results demonstrate that TF has potential ability to protect liver against NAFLD by regulating lipids metabolism and alleviating insulin resistance, inflammation and oxidative stress. This effect might be associated with regulating PPARα and CYP2E1 expression.

Abstract 6260: Up-Regulated Expression of MicroRNA-143 in Association with Obesity in the Adipose Tissue of Mice Fed High Fat Diet

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rieko Takanabe ◽  
Koh Ono ◽  
Tomohide Takaya ◽  
Takahiro Horie ◽  
Hiromichi Wada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Control Cell ◽  
High Fat ◽  
Expression Levels ◽  
Mesenteric Fat ◽  
Regulated Expression

Obesity is the result of an expansion and increase in the number of individual adipocytes. Since changes in gene expression during adipocyte differentiation and hypertrophy are closely associated with insulin resistance and cardiovascular diseases, further insight into the molecular basis of obesity is needed to better understand obesity-associated diseases. MicroRNAs (miRNAs) are approximately 17–24nt single stranded RNA, that post-transcriptionally regulate gene expression. MiRNAs control cell growth, differentiation and metabolism, and may be also involved in pathogenesis and pathophysiology of diseases. It has been proposed that miR-143 plays a role in the differentiation of preadipocytes into mature adipocytes in culture. However, regulated expression of miR-143 in the adult adipose tissue during the development of obesity in vivo is unknown. To solve this problem, C57BL/6 mice were fed with either high-fat diet (HFD) or normal chow (NC). Eight weeks later, severe insulin resistance was observed in mice on HFD. Body weight increased by 35% and the mesenteric fat weight increased by 3.3-fold in HFD mice compared with NC mice. We measured expression levels of miR-143 in the mesenteric fat tissue by real-time PCR and normalized with those of 5S ribosomal RNA. Expression of miR-143 in the mesenteric fat was significantly up-regulated (3.3-fold, p<0.05) in HFD mice compared to NC mice. MiR-143 expression levels were positively correlated with body weight (R=0.577, p=0.0011) and the mesenteric fat weight (R=0.608, p=0.0005). We also measured expression levels in the mesenteric fat of PPARγ and AP2, whose expression are deeply involved in the development of obesity, insulin resistant and arteriosclerosis. The expression levels of miR-143 were closely correlated with those of PPARγ (R=0.600, p=0.0040) and AP2 (R=0.630, p=0.0022). These findings provide the first evidence for up-regulated expression of miR-143 in the mesenteric fat of HFD-induced obese mice, which might contribute to regulated expression of genes involved in the pathophysiology of obesity.

scholarly journals CaMKIV limits metabolic damage through induction of hepatic autophagy by CREB in obese mice

2020 ◽  
Vol 244 (2) ◽  
pp. 353-367 ◽  
Author(s):  
Jiali Liu ◽  
Yue Li ◽  
Xiaoyan Zhou ◽  
Xi Zhang ◽  
Hao Meng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Inflammatory Response ◽  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Insulin Action ◽  
Hepatic Insulin Resistance ◽  
Obese Mice ◽  
High Fat ◽  
Impaired Insulin

High-fat diet (HFD) not only induces insulin resistance in liver, but also causes autophagic imbalance and metabolic disorders, increases chronic inflammatory response and induces mitochondrial dysfunction. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has recently emerged as an important regulator of glucose metabolism and skeletal muscle insulin action. Its activation has been involved in the improvement of hepatic and adipose insulin action. But the underlying mechanism is not fully understood. In the present study, we aimed to address the direct effects of CaMKIV in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. Our results indicated obese mice receiving CaMKIV showed decreased blood glucose and serum insulin and improved insulin sensitivity as well as increased glucose tolerance compared with vehicle injection. Meanwhile, defective hepatic autophagy activity, impaired insulin signaling, increased inflammatory response and mitochondrial dysfunction in liver tissues which are induced by high-fat diet were also effectively alleviated by injection of CaMKIV. Consistent with these results, the addition of CaMKIV to the culture medium of BNL cl.2 hepatocytes markedly restored palmitate-induced hepatic insulin resistance and autophagic imbalance. These effects were nullified by blockade of cyclic AMP response element-binding protein (CREB), indicating the causative role of CREB in action of CaMKIV. Our findings suggested that CaMKIV restores hepatic autophagic imbalance and improves impaired insulin sensitivity via phosphorylated CREB signaling pathway, which may offer novel opportunities for treatment of obesity and diabetes.

scholarly journals Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1598-1610 ◽  
Author(s):  
Maria M. Glavas ◽  
Melissa A. Kirigiti ◽  
Xiao Q. Xiao ◽  
Pablo J. Enriori ◽  
Sarah K. Fisher ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
Leptin Resistance ◽  
Signal Transducer ◽  
High Fat ◽  
Insulin Tolerance ◽  
Obesity And Diabetes ◽  
Transcription 3

Childhood obesity increases the risk of adult obesity and diabetes, suggesting that early overnutrition permanently programs altered energy and glucose homeostasis. In the present studies, we used a mouse model to investigate whether early overnutrition increases susceptibility to obesity and insulin resistance in response to a high-fat diet (HFD). Litters from Swiss Webster dams were culled to three [chronic postnatal overnutrition (CPO)] or 10 (control) pups and then weaned onto standard chow at postnatal day (P) 23. At 6 wk of age, a subset of mice was placed on HFD, and glucose and insulin tolerance were examined at 16–17 wk of age. Leptin sensitivity was determined by hypothalamic phosphorylated signal transducer and activator of transcription-3 immunoreactivity at P16 and adulthood after ip leptin. CPO mice exhibited accelerated body weight gain and hyperleptinemia during the preweaning period but only a slightly heavier body weight and normal glucose tolerance in adulthood on standard chow diet. Importantly, CPO mice exhibited significant leptin resistance in the arcuate nucleus, demonstrated by reduced activation of phospho-signal transducer and activator of transcription-3, as early as P16 and throughout life, despite normalized leptin levels. In response to HFD, CPO but not control mice displayed insulin resistance in response to an insulin tolerance test. In conclusion, CPO mice exhibited early and persistent leptin resistance in the arcuate nucleus and, in response to HFD, rapid development of obesity and insulin resistance. These studies suggest that early overnutrition can permanently alter energy homeostasis and significantly increase susceptibility to obesity and insulin resistance.

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