Celastrol Ameliorates Liver Metabolic Damage Caused By A High-fat Diet Through SIRT1

SIRT1 may be a new therapeutic target for the prevention of non-alcoholic fatty liver disease(NAFLD).Here,treatment of wild-type mice on high fat diet with Celastrol,a traditional Chinese medicine,decreased body weight,subcutaneous and visceral fat content,and liver lipid droplet formation,and reduced hepatic intracellular triglyceride and serum triglyceride,free fatty acid and ALT concentration.These effects may be owing to Celastrol increasing SIRT1 expression,further decreasing sterol regulatory element binding protein 1c(SREBP-1c)expression and improving anti-inflammatory and antioxidant states in liver.However,these Celastrol-mediated effects were abolished in SIRT1-deficient mice.Additionally,Celastrol obviously promoted liver lipid droplet formation in SIRT1-deficient mice on high fat diet.Furthermore,Celastrol repressed HDAC3 expression in WT and SIRT1-deficient mice,resulting in the increase of NF?B activity and inflammatory states in SIRT1-deficient mice.