Effects Of Exercise And Dietary Intervention On The Pancreatic Nesfatin-1 /AMPK/mTOR Pathway In Obese Mice

Objective:The research is designed to explore the influence of exercise and dietary interventions on pancreas Nesfatin-1 and its downstream AMPK/mTOR pathway in insulin-resistant mice,which induced by high-fat diet,in order to reveal the role of exercise and dietary interventions in the mechanism of improving insulin resistance and provide experimental basis.Methods:80 Male C57BL/6 mice,4 weeks old,were randomly divided in Control group?C group?which fed by normal feed,and High fat group?HF?,that fed by high fat feed.By fed for 8 weeks,the fat mice had a weight of 120%of the normal weight group,all the fat mice were divided into 7groups:High fat diet group?HF group?,70%High fat diet group(HF_70%group),HF+High intense exercise group(HFE,HF_70%+High intense exercise group(HFE_70%,),HF+Nesfatin-1 group?NHF?,HF_70%+Nesfatin-1 group(NHF_70%),HF_70%+High intense exercise+Nesfatin-1 group?HFEN?.The3 Nesfatin-1 injection groups were injected with Nesfatin-1 in a dose?15ug/BW/d?for the last three days of intervention consecutively,and the control groups were injected with the same dose of physiological saline,the biological sample was taken after 12h of the last injection.The blood indicators including blood glucose,blood lipid?TG?and insulin were measured by ELISA measurement.Nesfatin-1,AMPK and mTOR protein and gene expression level were tested respectively by Western Blot and Real time qPCR.SPSS 19.0 statistical processing software was used to analyze the data obtained from each test index,and the mean number and/or standard deviation?s?indicated the experimental results.Single factor variance analysis was used to determine whether there were significant differences between groups.Results:1.In obese mice,the weight and blood lipid concentration increased significantly,and fasting glucose and insulin concentration increased significantly as well?p<0.01,p<0.01,p<0.01,p<0.05?.The gene and protein expression levels of Nesfatin-1 and AMPK/mTOR were significantly decreased in the pancreas of obese mice?p<0.01,p<0.05,p<0.05,p<0.05,p<0.05,p<0.05?.After exogenous injection of nesfatin-1,the gene and protein expression levels of AMPK/mTOR in the pancreas of each group were significantly increased?p<0.05,p<0.05,p<0.05,p<0.05?,and blood glucose,blood TG and insulin levels also decreased significantly?p<0.05,p<0.05,p<0.01?.2.Ether single exercise intervention or single diet intervention,or common intervention by both exercise and diet could decrease body weight,blood lipids,blood glucose and serum insulin levels significantly?p<0.05,p<0.05,p<0.01?,meanwhile improve gene and protein expression of Nesfatin-1?AMPK and mTOR in obese mice pancreas?p<0.05,p<0.01,p<0.01?.Conclusion:1.High-fat diet could cause severe obesity and insulin resistance in mice,and its mechanism is related to the inhibition of pancreatic Nesfatin-1/AMPK/mTOR pathway.2.Single intervention of diet or exercise could significantly improve the obesity and insulin resistance in mice,and its mechanism is related to the activation of Nesfatin-1/AMPK/mTOR pathway.Both diet and exercise intervention could significantly activate the Nesfatin-1/AMPK/mTOR pathway,thereby relieve obesity and insulin resistance.