关键词: 法尼醇受体, 高脂饮食, 糖脂代谢, 肝脏脂肪变性

Abstract: Objective To investigate the effects of high fat diet on glycolipid metabolism and hepatic steatosis in farnesoid X receptor ( FXR) knockout mice. Method Normal diet ( ND ) group : C57BL/6 ( wild type, WT) mice (n = 6 ) and FXR 7 mice ( n = 6) were given normal diet for 12 weeks. High fat diet ( HFD ) group : C57BL/6mice (n = 6) and FXR / mice ( n = 6 ) were given 45% high fat diet for 12 weeks. After the mice were sacrificed, serum total cholesterol ( TC ) , triglyceride ( TG) , low density lipoprotein cholesterol ( LDL-C ) , high density lipoprotein cholesterol ( HDL-C ) , alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) and total bile acid (TBA) indicators were detected by automatic biochemical analyzer. The expression levels of liver inflammatory genes TNF-a, TLR4 and the downstream genes of FXR small heterodimer partner ( SHP ) , cholesterol 7 &-hydroxylase ( CYP7A1 ) were determined by RT-PCR. Liver steatosis was observed by HE staining. Result There was no difference in body weight between C57BL/6 mice and FXR / mice under high fat diet, but FXR / mice showed more severe glucose tolerance than C57BL/6 mice ( P<0. 01) , lipid metabolism disorder ( P<0. 01 ), serum bile acid increase (1<0. 01) , liver inflammation (1<0. 01) and hepatic steatosis. Conclusion Deletion of FXR caused disordersofglucoseand lipid metabolism , abnormalbileacid metabolism and hepaticsteatosisin mice , but that required induction of high fat diet.

Key words: Farnesoid X receptor , high fat diet, glycolipid metabolism , Hepatic steatosis