scholarly journals The Immunomodulating Effect of Baicalin on Inflammation and Insulin Resistance in High-Fat-Diet-Induced Obese Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ji-Won Noh ◽  
Oh-Jun Kwon ◽  
Byung-Cheol Lee
Keyword(s):  
Insulin Resistance ◽  
Immune Cells ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Liver Weight ◽  
Tolerance Test ◽  
The Body ◽  
High Fat ◽  
Normal Chow ◽  
Anti Inflammatory

Background. Obesity is a chronic low-grade systemic inflammation state, which causes insulin resistance, diabetes, and other metabolic diseases. Baicalin is known to have anti-inflammatory and antiobesity effects. In this study, we investigated the cellular and molecular immunological effects of baicalin on obesity-induced inflammation. Methods. Male C57BL/6 mice were assigned to four groups: the normal chow, high-fat diet (HFD), BC2 (HFD + baicalin 200 mg/kg), and BC4 (HFD + baicalin 400 mg/kg) group; the three groups except normal chow were fed with a high-fat diet for 8 weeks to induce obesity followed by baicalin treatment with two doses for 8 weeks. The body weight, epididymal fat weight, liver weight, food intake, oral glucose tolerance test (OGTT), oral fat tolerance test (OFTT), and serum lipids were measured. We evaluated insulin resistance by measuring the serum insulin level and homeostatic model assessment of insulin resistance (HOMA-IR). Also, the major obesity-associated immune cells including monocytes, macrophages, T lymphocytes, and dendritic cells in the blood, fat, and liver and the inflammatory and insulin signaling-related gene expressions in the fat and liver were evaluated. Results. Baicalin significantly reduced the body weight and liver weight and improved serum fasting glucose, insulin, HOMA-IR, free fatty acid, HDL cholesterol, and the levels of glucose and triglyceride at each time point in the OGTT and OFTT. In the analysis of immune cells, baicalin significantly decreased inflammatory Ly6Chi monocytes, M1 adipose tissue macrophages (ATMs), and M1 Kupffer cells. On the contrary, baicalin increased anti-inflammatory M2 ATMs and liver CD4+ T cells and CD4/CD8 ratio. In the analysis of inflammatory and insulin signaling molecules, baicalin significantly downregulated the gene expression of tumor necrosis factor-α, F4/80, and C-C motif chemokine 2 while upregulated the insulin receptor mRNA expression. Conclusion. From these results, baicalin can be a promising treatment option for obesity and its related metabolic diseases based on its anti-inflammatory property.

scholarly journals ADAR1 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

2020 ◽  
Author(s):  
Xiaobing Cui ◽  
Jia Fei ◽  
Sisi Chen ◽  
Gaylen L. Edwards ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Food Intake ◽  
High Fat Diet ◽  
Peptide Yy ◽  
Tolerance Test ◽  
Chow Diet ◽  
High Fat ◽  
Blood Biochemical ◽  
Insulin Tolerance ◽  
Normal Chow

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases, and many other chronic diseases. The objective of this study was to determine the role of adenosine deaminase acting on RNA 1 (ADAR1) in the development of obesity and insulin resistance. Wild-type (WT) and heterozygous ADAR1-deficient (Adar1+/-) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Adar1+/- mice fed with HFD exhibited a lean phenotype with reduced fat mass compared with WT controls, although no difference was found under chow diet conditions. Blood biochemical analysis and insulin tolerance test showed that Adar1+/- improved HFD-induced dyslipidemia and insulin resistance. Metabolic studies showed that food intake was decreased in Adar1+/- mice compared with the WT mice under HFD conditions. Paired feeding studies further demonstrated that Adar1+/- protected mice from HFD-induced obesity through decreased food intake. Furthermore, Adar1+/- restored the increased ghrelin expression in stomach and the decreased serum peptide YY levels under HFD conditions. These data indicate that ADAR1 may contribute to diet-induce obesity, at least partially, through modulating the ghrelin and peptide YY expression and secretion.

Improvement on Lipid Metabolic Disorder by 3′-Deoxyadenosine in High-Fat-Diet-Induced Fatty Mice

2010 ◽  
Vol 38 (06) ◽  
pp. 1065-1075 ◽  
Author(s):  
Ya-Jing Niu ◽  
Rong-Ya Tao ◽  
Qian Liu ◽  
Jin-Ying Tian ◽  
Fei Ye ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
High Fat Diet ◽  
Metabolic Disorder ◽  
Tolerance Test ◽  
The Body ◽  
Oral Glucose ◽  
Model Assessment ◽  
High Fat ◽  
Lipid Metabolic Disorder

This study explores the effects of 3′-deoxyadenosine, a compound from Cordyceps militaris, on lipid metabolic disorder induced by a high-fat-diet in C57BL/6 mice. These mice had an obese body, lipid metabolic disorder and insulin resistance and were treated orally with 100 mg/kg/day 3′-deoxyadenosine (DA), 15 mg/kg/day rosiglitazone and 150 mg/kg/day fenofibrate, respectively. Compared to the model mice, the body weight gain in DA-treated mice were decreased by 66.5%, serum triglyceride and total cholesterol levels were decreased by 20.7% and 16.7%, respectively, and the triglyceride content in the skeletal muscle was reduced by 41.2%. This treatment also had a significant effect on insulin resistance. In DA-treated mice, the serum insulin levels and homeostasis model assessment of the insulin resistance index were decreased by 30% and 46%, respectively, and the areas under the glucose-time curve were depressed by 18% in the insulin tolerance test and by 21.5% in the oral glucose tolerance test. Finally, the value of glucose infusion rates and insulin induced-glucose uptake into the skeletal muscle in the hyperinsulinemic-euglycemic clamp test were increased by 18% and 41%, respectively, compared to those in the model mice. This data suggests that the effects of DA on lipid metabolic disorder induced by a high-fat-diet may be linked to its improvement on insulin resistance, especially concerning the increase of insulin sensitivity in the skeletal muscle.

scholarly journals Dietary Administration of 2-Deoxy-D-Glucose Reduces High Fat Diet Induced Obesity and meta-inflammation in Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 920-920
Author(s):  
Sanjay Pandey Diksha Joshi ◽  
Saurabh Singh ◽  
Sushma Ray ◽  
Anant Narayan Bhatt ◽  
K Natarajan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Liver Weight ◽  
Energy Restriction ◽  
Lipid Levels ◽  
High Fat ◽  
Tissue Mass

Abstract Obesity is a major risk factor for type 2 diabetes, NAFLD, chronic diseases and cancer. Insulin resistance, oxidative stress, high ectopic lipid levels and meta-inflammation are the mechanisms proposed to play a leading role in the morbidity associated with obesity. Energy restriction mimetics (ERMAs) has also been shown earlier to reduce the scale and the severity of these disorders by mimicking the physiological effects of the Energy Restriction. In present study we propose that the use of 2-DG as ERMA can be effective in regulating the High Fat Diet (HFD) induced obesity. Effect of 2-DG (0.4% w/v in drinking water) on the HFD and Insulin Resistance (IR). HFD induced change in body weight, adipose tissue mass, and ectopic lipid levels was assessed as the measure of obesity.IR and glucose levels were also estimated to evaluate the effect of 2-DG on the insulin sensitivity in HFD mice. 2-DG significantly altered HFD induced increase in the mice body weight, epididymal White Adipose Tissue (WAT) and liver weight. 2-DG fed mice also showed reduced lipid levels in serum and liver. Furthermore, 2-DG also reduced the oxidative damage in the liver with concomitant increase in enzymatic (SOD and Catalase) and non-enzymatic (reduced Glutathione) antioxidant levels. 2-DG fed mice also showed reduced levels of Leptin, IL-6 and TGF-β which are early drivers of the etiology of the metabolic diseases. Our results suggest that 2-DG as ERMA can prevent obesity and etiology of associated disorders. However, more relevant models are needed to further strengthen these observation

scholarly journals Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2109-2117 ◽  
Author(s):  
Elodie Riant ◽  
Aurélie Waget ◽  
Haude Cogo ◽  
Jean-François Arnal ◽  
Rémy Burcelin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Normal Chow ◽  
Visceral Adipose ◽  
Deficient Mice ◽  
Normal Chow Diet

Although corroborating data indicate that estrogens influence glucose metabolism through the activation of the estrogen receptor α (ERα), it has not been established whether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat diet (HFD). To this end, we first evaluated the influence of chronic 17β-estradiol (E2) administration in wild-type ovariectomized mice submitted to either a normal chow diet or a HFD. Whereas only a modest effect was observed in normal chow diet-fed mice, E2 administration exerted a protective effect against HFD-induced glucose intolerance, and this beneficial action was abolished in ERα-deficient mice. Furthermore, E2 treatment reduced HFD-induced insulin resistance by 50% during hyperinsulinemic euglycemic clamp studies and improved insulin signaling (Akt phosphorylation) in insulin-stimulated skeletal muscles. Unexpectedly, we found that E2 treatment enhanced cytokine (IL-6, TNF-α) and plasminogen activator inhibitor-1 mRNA expression induced by HFD in the liver and visceral adipose tissue. Interestingly, although the proinflammatory effect of E2 was abolished in visceral adipose tissue from chimeric mice grafted with bone marrow cells from ERα-deficient mice, the beneficial effect of the hormone on glucose tolerance was not altered, suggesting that the metabolic and inflammatory effects of estrogens can be dissociated. Eventually comparison of sham-operated with ovariectomized HFD-fed mice demonstrated that endogenous estrogens levels are sufficient to exert a full protective effect against insulin resistance and glucose intolerance. In conclusion, the regulation of the ERα pathway could represent an effective strategy to reduce the impact of high-fat diet-induced type 2 diabetes.

scholarly journals Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

2020 ◽  
Vol 295 (31) ◽  
pp. 10842-10856 ◽  
Author(s):  
Wen Liu ◽  
Ye Yin ◽  
Meijing Wang ◽  
Ting Fan ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Low Grade ◽  
High Fat ◽  
Caspase 1

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

scholarly journals Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

2014 ◽  
Vol 307 (3) ◽  
pp. R332-R339 ◽  
Author(s):  
Jieyun Yin ◽  
Jian Kuang ◽  
Manisha Chandalia ◽  
Demidmaa Tuvdendorj ◽  
Batbayar Tumurbaatar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

scholarly journals Preventive Effects of Kaempferol on High-Fat Diet-Induced Obesity Complications in C57BL/6 Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Tieqiao Wang ◽  
Qiaomin Wu ◽  
Tingqi Zhao
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Blood Glucose ◽  
Gut Microbiota ◽  
Serum Cholesterol ◽  
High Fat Diet ◽  
Liver Weight ◽  
Control Group ◽  
High Fat ◽  
High Blood Glucose

Kaempferol is a dietary flavanol that regulates cellular lipid and glucose metabolism. Its mechanism of action in preventing hepatic steatosis and obesity-related disorders has yet to be clarified. The purpose of this research was to examine kaempferol’s antiobesity effects in high-fat diet- (HFD-) fed mice and to investigate its impact on their gut microbiota. Using a completely randomized design, 30 mice were equally assigned to a control group, receiving a low-fat diet, an HFD group, receiving a high-fat diet, and an HFD+kaempferol group, receiving a high-fat diet and kaempferol doses of 200 mg/kg in the diet. After eight weeks, the HFD mice displayed substantial body and liver weight gain and high blood glucose and serum cholesterol levels. However, treatment with kaempferol moderated body and liver weight gain and elevation of blood glucose and serum cholesterol and triglyceride levels. Examination of 16S ribosomal RNA showed that HFD mice exhibited decreased microbial diversity, but kaempferol treatment maintained it to nearly the same levels as those in the control group. In conclusion, kaempferol can protect against obesity and insulin resistance in mice on a high-fat diet, partly through regulating their gut microbiota and moderating the decrease in insulin resistance.

scholarly journals Melatonin Improves Glucose Homeostasis and Endothelial Vascular Function in High-Fat Diet-Fed Insulin-Resistant Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5311-5317 ◽  
Author(s):  
Claudio Sartori ◽  
Pierre Dessen ◽  
Caroline Mathieu ◽  
Anita Monney ◽  
Jonathan Bloch ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Signal Transduction ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
High Fat ◽  
Insulin Resistant ◽  
Normal Chow ◽  
Underlying Mechanisms

Abstract Obesity and insulin resistance represent a problem of utmost clinical significance worldwide. Insulin-resistant states are characterized by the inability of insulin to induce proper signal transduction leading to defective glucose uptake in skeletal muscle tissue and impaired insulin-induced vasodilation. In various pathophysiological models, melatonin interacts with crucial molecules of the insulin signaling pathway, but its effects on glucose homeostasis are not known. In a diet-induced mouse model of insulin resistance and normal chow-fed control mice, we sought to assess the effects of an 8-wk oral treatment with melatonin on insulin and glucose tolerance and to understand underlying mechanisms. In high-fat diet-fed mice, but not in normal chow-fed control mice, melatonin significantly improved insulin sensitivity and glucose tolerance, as evidenced by a higher rate of glucose infusion to maintain euglycemia during hyperinsulinemic clamp studies and an attenuated hyperglycemic response to an ip glucose challenge. Regarding underlying mechanisms, we found that melatonin restored insulin-induced vasodilation to skeletal muscle, a major site of glucose utilization. This was due, at least in part, to the improvement of insulin signal transduction in the vasculature, as evidenced by increased insulin-induced phosphorylation of Akt and endoethelial nitric oxide synthase in aortas harvested from melatonin-treated high-fat diet-fed mice. In contrast, melatonin had no effect on the ability of insulin to promote glucose uptake in skeletal muscle tissue in vitro. These data demonstrate for the first time that in a diet-induced rodent model of insulin resistance, melatonin improves glucose homeostasis by restoring the vascular action of insulin.

scholarly journals Cytochrome P-450 CYP2E1 knockout mice are protected against high-fat diet-induced obesity and insulin resistance

2012 ◽  
Vol 302 (5) ◽  
pp. E532-E539 ◽  
Author(s):  
Haihong Zong ◽  
Michal Armoni ◽  
Chava Harel ◽  
Eddy Karnieli ◽  
Jeffrey E. Pessin
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Whole Body ◽  
High Fat ◽  
Normal Chow ◽  
Glucose Output ◽  
Fat Diets

Conventional (whole body) CYP2E1 knockout mice displayed protection against high-fat diet-induced weight gain, obesity, and hyperlipidemia with increased energy expenditure despite normal food intake and spontaneous locomotor activity. In addition, the CYP2E1 knockout mice displayed a marked improvement in glucose tolerance on both normal chow and high-fat diets. Euglycemic-hyperinsulinemic clamps demonstrated a marked protection against high-fat diet-induced insulin resistance in CYP2E1 knockout mice, with enhanced adipose tissue glucose uptake and insulin suppression of hepatic glucose output. In parallel, adipose tissue was protected against high-fat diet-induced proinflammatory cytokine production. Taken together, these data demonstrate that the CYP2E1 deletion protects mice against high-fat diet-induced insulin resistance with improved glucose homeostasis in vivo.

scholarly journals Ganoderma lucidum Extract Reduces Insulin Resistance by Enhancing AMPK Activation in High-Fat Diet-Induced Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3338
Author(s):  
Hyeon A Lee ◽  
Jae-Han Cho ◽  
Qonita Afinanisa ◽  
Gi-Hong An ◽  
Jae-Gu Han ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
High Fat Diet ◽  
Ganoderma Lucidum ◽  
Fatty Acid Synthase ◽  
Metabolic Diseases ◽  
Ampk Activation ◽  
High Fat ◽  
Amp Activated Protein Kinase

Ganoderma lucidum is used widely in oriental medicine to treat obesity and metabolic diseases. Bioactive substances extracted from G. lucidum have been shown to ameliorate dyslipidemia, insulin resistance, and type 2 diabetes in mice via multiple 5′ AMP-activated protein kinase (AMPK)-mediated mechanisms; however, further studies are required to elucidate the anti-obesity effects of G. lucidum in vivo. In this study, we demonstrated that 3% G. lucidum extract powder (GEP) can be used to prevent obesity and insulin resistance in a mouse model. C57BL/6 mice were provided with a normal diet (ND) or a high-fat diet (HFD) supplemented with 1, 3, or 5% GEP for 12 weeks and the effect of GEP on body weight, liver, adipose tissue, adipokines, insulin and glucose tolerance (ITT and GTT), glucose uptake, glucose-metabolism related proteins, and lipogenesis related genes was examined. GEP administration was found to reduce weight gain in the liver and fat tissues of the mice. In addition, serum parameters were significantly lower in the 3% and 5% GEP mice groups than in those fed a HFD alone, whereas adiponectin levels were significantly higher. We also observed that GEP improved glucose metabolism, reduced lipid accumulation in the liver, and reduced adipocyte size. These effects may have been mediated by enhanced AMPK activation, which attenuated the transcription and translation of lipogenic genes such as fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1), and sterol regulatory element-binding protein-1c (SREBP1c). Moreover, AMP-activated protein kinase (AMPK) activation increased acetyl-CoA carboxylase (ACC), insulin receptor (IR), IR substrate 1 (IRS1), and Akt protein expression and activation, as well as glucose transporter type 1/4 (GLUT1/4) protein production, thereby improving insulin sensitivity and glucose metabolism. Together, these findings demonstrate that G. lucidum may effectively prevent obesity and suppress obesity-induced insulin resistance via AMPK activation.

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