Regulation And Mechanism Of Every Other Day Fasting On Lipid Metabolism Homeostasis

Background and Aims: Unhealthy life style is a key risk for people suffering from non-alcoholic hepatic steatosis.Previous studies have showed that acute fasting can induce obvious hepatic steatosis.However,intermittent fasting has been reported to benefit healthy and even extend lifespan.So the aim of this study is to explore the role and the potential mechanism of every other day fasting(EOD)for acute fasting-induced steatosis.Methods: The C57BL/6 mice were proceed to acute fasting for 24 hours after a period of ad libitum(AL)and EOD cycles.Then the liver and serum were isolated for biochemical and molecular assays,with a focus on the regulation and mechanism of EOD for lipid metabolism homeostasis.Results:(1)When compared with the AL group,EOD did significantly reduce the body mass gain during 17 cycles of EOD treatment.Compared with fed state,24 h acute fasting dramatically decreased the liver index and increased the serum alanine aminotransferase.Moreover,after 24 h acute fasting,obvious lipid droplets occurred in the liver sections of AL mice,while not in EOD mice.(2)Further analyses indicated that EOD treatment significantly reduced liver triglyceride,while evaluated serum insulin and hepatic glycogen.The expression of related metabolic genes illustrated that EOD suppressed Ppar? and Glut4 expression in fed state.However,in fasted state,EOD upregulated the expression of genes responsible for lipid metabolism(Ppara,Fgf21,Cpt1 a and Hmgcs2),while downregulated the expression of genes for glucose metabolism(Glut4?Pgc1a and Pygl).(3)In fed state,EOD ameliorated serum malondialidehyde levels,and increased total antioxidant capacity.After 24 h acute fasting,hepatic malondialidehyde levels increased obviously in AL mice,while EOD suppressed the increment.Conclusions:(1)EOD treatment can reduce body mass gain,elevate serum insulin level,and subsequently promote glycogen synthesis while inhibit lipid mobilization.(2)EOD decreased the level of malondialdehyde but increased the activity of superoxide dismutase and glutathione peroxidase.(3)Therefore,EOD might alleviate hepatic steatosis through promoting glucose metabolism,suppressing lipid metabolism,and reducing oxidative stress and liver injury.