Expression Of SIK1in The Non-alcoholic Fatty Liver In Type2Diabetic Rats And Intervention Effects Of Zhenqing Recipe

Background and Objective： Salt-inducible kinase1(SIK1), a member of theAMP-activated protein kinase (AMPK) family, directly regulates sterol regulatory elementbinding-protein-1c (SREBP-1c)-dependent hepatic lipogenesis. We observed theexpression of SIK1on non-alcoholic fatty liver in type2diabetic rats, and examined theeffects of Zhenqing Recipe (ZQR), a Chinese herbal medicine, on hepatic SIK1.Methods：An animal model of type2diabetes was established by high fat/sucrose dietcombined with streptozotocin injections. The diabetic rats were randomly divided intountreated diabetic, ZQR and metformin group. Normal rats served as control. ZQR(8g/kg/day, i.g.) or metformin(10mg/kg/day, i.g.) was orally administered for12weeks.Then, the levels of fasting blood glucose (FBG), serum triglyceride (TG)，serum totalcholesterol (TC)， serum alanine aminotransferase(ALT), aspartate aminotransferase（AST）,liver TG content and index of liver in each group were tested. Meanwhile,pathological changes of liver, the expression of SIK1mRNA and protein, SREBP-1cmRNAand protein, SIK1protein of liver tissues in each group were detected.Results：After treatment for twelve-week, the serum glucose, TC, TG, ALT,AST, index ofliver and liver TG content in untreated diabetic rats were significantly higher than that of normal control rats（P<0.01或P<0.05）. ZQR treatment not only reduced serum glucoselevel in diabetic rats, but also decreased TC and TG were significantly decreased in ZQRgroups compared with untreated diabetic group（P<0.01，P<0.05）. Histopathological studyof liver showed that liver cirrhosis in diabetic rats was significantly improved in ZQRgroup. Compared with the control group, both mRNA and protein levels of SIK1weresignificantly decreased （P<0.01）,while SREBP-1c mRNA and protein expression wereelevated in the liver of untreated diabetic rats（P<0.01）. ZQR significantly increased SIK1mRNA and protein expression, in contrast,SREBP-1c mRNA and protein expression werereduced in ZQR groups （P<0.01）. Consequently, liver triglyceride was significantlyreduced in ZQR groups（P<0.01）. The administration of ZQR significantly increased themRNAand protein levels of hepatic SIK1.Conclusions：The expression of SIK1is lowered in non-alcoholic fatty liver with type2diabetic rats, ZQR alleviates non-alcoholic fatty liver by up-regulating hepatic SIK1at themRNAand protein level.