Resveratrol Improves High Fat Diet Induced Insulin Resistance And Fatty Liver In Mice

Objective:To explore the establishment of diabetic mice model.Methods:30 male C57BL/6J mice were randomly divided into normal control group(NC, n=15) and high fat diet(HF,n=15) group.HF group were fed with high fat diet,while the NC group were fed with standard chow diet.All mice received IPGTT in the end of 8 weeks and 24 weeks to evaluate it glucose metabolism.And the plasma free fatty acid (FFA),plasma triglyceride(TG),plasma cholesterol(Chol) and plasma insulin of HF mice were measured.ISI and insulin resistance index were calculated according to the plasma glucose and plasma insulin.Results:24 weeks later,The plasma glucose at Omin,30min,60min and 120min of HF mice were 1.3 times,1.4 times,1.4 times and 1.2 times those of NC group(P<0.01), respectively.Compared with NC group,plasma FFA,TG and Chol of HF mice were also increased and the differences between them had the statistical significance(P<0.01). Compared with NC group,ISI of HF mice were decreased(P<0.01) while the insulin resistance index were increased(P<0.01).Conclusions:The high-fat diet-fed C57BL/6J mouse model is a robust model for type 2 diabetes.The diabetic model that induced by the high fat diet have the characteristics of obesity,hyperglycemia,dyslipidemia,insulin resistance(IR) and hyperinsulinemia. Obojective:To observe the effects of resveratrol on insulin resistance(IR) and explore its related mechanisms.Method:45 male C57BL/6J mice were randomly allocated to three groups(15 mice for each group):normal control group(NC group,fed with standard chow),high fat feeding group(HF group,fed with high fat diet) and resveratrol treated group(HR group).The resveratrol-treated group was fed with high fat diet all the time and received resveratrol administration(400mg/kg.day) except the first 8 weeks.Each group mice were kept 24 weeks before killed.At the end of animal experiment,mice were sacrificed and adipose tissue and liver collected.Weight,blood glucose,insulin were measured,and visceral fat were weighted.Hematoxylin and eosin(HE) staining was used to evaluate pathology changes in visceral fat.ATGL,PGC-1αmRNA and ATGL protein were measured in visceral fat.And also PEPCK,G-6-Pase and FoxOlmRNA expression,involved in gluconeogenesis,were measured.ResultsCompared to NC group,weight and visceral fat index were increased in HF group. Fasting serum insulin(FINS) was elevated and fasting blood glucose was increased in HF group.ATGL protein levels in WAT in HF group equaled to NC group.However, resveratrol administration greatly improved the visceral fat index,FBG,FINS compared with HF group.Compare with NC group,ATGL protein levels in HR group were elevated to 126.9%with the up-regulation of ATGL mRNA expressions in WAT.Compared with NC group,the levels of FoxO1,PEPCK,G-6-Pase in the liver were increased to 135.6%, 154.8%,and 164.7%,respectively(P<0.05) in HF group and decreased to 108.4%, 105.5%,110.3%(P<0.05).Conclusions:Resveratrol administration markedly improved high-fat feeding induced insulin resistance.Administration of resveratrol can result in weight and blood glucose reduction.Elevated expression of ATGL may contribute to the improvement of obesity. Elevated expression of PGC-la can increase fat oxidation.High fat diet induced liver expressions of FoxOl,PEPCK,G-6-Pase,thus promote gluconeogenesis,resulting in higher FBG.Resveratrol can reduce liver expressions of FoxOl,PEPCK,G-6-Pase, strengthen insulin signal conduction,suppress gluconeogenesis and thus regulate glycometabolism. Obojective:To explore the improvement effects of resveratrol on nonalcoholic fatty liver induced by high fat diet,and related mechanisms.Method:45 male C57BL/6J mice were randomly allocated to three groups(15 mice for each group):normal control group(NC group,fed with standard chow),high fat feeding group(HF group,fed with high fat diet) and resveratrol treated group(HR group).The resveratrol-treated group was fed with high fat diet all the time and received resveratrol administration(400mg/kg.day) except the first 8 weeks.Each group mice were kept 24 weeks before killed.At the end of animal experiment,mice were sacrificed and liver pathology changes were measured.RT-PCR was used to detect ATGL and PGC-1αmRNA expressions.WesternBlot was used to measure ATGL protein expression.Results Compared to NC group,Pathology of liver steatosis was observed in light microscope in HF group.ATGL protein levels in HR group were elevated to 135.8%with the up-regulation of ATGL mRNA expressions in liver.The mRNA expression of PGC-1αwere significantly lower in HF group than those in HR group(P<0.01).Conclusions:Administration of resveratrol can promote ATGL expression in fatty liver. Elevated expression of ATGL may contribute to the improvement of fatty liver. Upregulation expression of PGC-la in the liver by resveratrol can result in elevation of lipolysis and fat oxidation.