Beneficial Effects And Underlying Mechanisms Of Intermittent Fasting On Glucose And Lipid Metabolism Disorders In Metabolic Syndrome Model Mice

With the development of social economy,modern dietary mode in which people have high calorie food at least three times daily increases the risk of metabolic disorders,such as obesity and diabetes,which become the main global health risks.Intermittent fasting is a novel approach contributing to effective body weight loss in obese individuls.In this process,water intake is free while regular periodic fasting is implemented.Previous research shows intermittent fasting relief chronic metabolic diseases caused by insulin resistance,However,there are few studies probe into the potential mechanism of intermittent fasting.In this study,we used obese mice and db/db mice,aimed at a futher understanding of the mechanisms how intermittent fasting promote body weight loss.The main investigations and results are as follows:(1)45% high fat diet induced obese C57BL/6J mice were used to investigate the effect of intermittent fasting on diet induced body weight gain and energy intake.Results showed that intermittent fasting reduces the level of obesity though increasing their energy intake,and improved plasma metabolic parameters such as TC,TG,HDL and LDL,decreased the level of AST,ALT,γ-GT while increased the level of ALB,promoted glucose and insulin tolerances of diet-induced obese mice;(2)In liver,intermittent fasting decreased the liver weight and the level of hepatic lilpid contents.The mRNA expressions of hepatic lipogenic such as Ppar-γ,Srebp1 c,Acaca,Fasn,Gck were significantly decressed by intermittent fasting.mRNA that regulate lipolysis and mitochondria biogenesis such as Ppar-α,Cpt1α,Cpt2,Pgc1α,Sirt1,Ucp4 were incressed.Moreover,intermittent fasting also attenuated cholesterol synthesis by downregulating cholesterol synthesis mRNA expressions of Hmgcr and Acat2.Western blot results showed that after intermittent fasting,phosphorylation level of AMPK and ULK were upregulated,and there is an obvious tendency of LC3-Ⅰ turning to LC3-Ⅱ,suggesting autophagy was increased,so that decreasing serum and hepatic lilpid contents and insulin resistance;(3)db/db mice were used to investigate the effects of intermittent fasting on db/db mice body weight gain and energy intake;Results showed that intermittent fasting reduces the level of obesity,improves plasma metabolic parameters such as TC,TG,HDL and LDL,decreased the level of AST,ALT,γ-GT while increased the level of ALB,promotes insulin tolerances of db/db mice;Moreover,intermittent fasting also promotes Insulin homeostasis by regulating protein expression;(4)In liver,intermittent fasting decreased the liver weight and the level of hepatic lilpid contents.phosphorylation level of ACC were upregulated,the protein expressions of SREBP1 c,PPAR-γ were significantly decressed by intermittent fasting.proteins that regulate mitochondria biogenesis such as ND1,PGC1α,SIRT1 were incressed.Western blot results also showed that after intermittent fasting,phosphorylation level of AMPK and ULK were upregulated and there is an obvious tendency of LC3-Ⅰ turning to LC3-Ⅱ,suggesting autophagy was increased,so that decreasing serum and hepatic lilpid contents and insulin resistance of db/db mice;This experiment reveals that short-term inermittent fasting has great effect on restoring healthy steady state function through autophagy in both diet-induced obese mice and db/db mice,which provides the basic theory for developmemt and clinical application of intermittent fasting.