高脂饮食对法尼醇受体(FXR)敲除小鼠糖脂代谢及肝脏脂肪变性的影响研究

目的探讨高脂饮食对法尼醇受体（farnesoid X receptor,FXR）敲除小鼠糖脂代谢及肝脏脂肪变性的影响。方法正常饮食（normal diet,ND）组:C57BL/6（wild type,WT）小鼠（n=6）和FXR -/- 小鼠（n=6）给予辐照灭菌维持饲料喂养12周。高脂饮食（high fat diet,HFD）组:C57BL/6小鼠（n=6）和FXR -/- 小鼠（n=6）给予45%高脂饲料喂养12周。小鼠处死后全自动生化分析仪检测血清总胆固醇（total cholesterol,TC）、甘油三酯（triglyceride,TG）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol,LDL-C）、高密度脂蛋白胆固醇（High density lipoprotein cholesterol,HDL-C）、谷丙转氨酶（alanine aminotransferase,ALT）、谷草转氨酶（aspartate aminotransferase,AST）和总胆汁酸（total bile acid,TBA）指标; RT-PCR检测肝脏炎症因子TNF-α、TLR4和FXR下游基因小分子异源二聚体（small heterodimer partner,SHP）、胆固醇7α-羟化酶（cholesterol 7α-hydroxylase,CYP7A1）的相对表达量; HE染色观察肝脏脂肪变性情况。结果高脂饮食喂养条件下,C57BL/6小鼠和FXR -/- 小鼠体质量变化无差异,但相比C57BL/6小鼠,FXR -/- 小鼠表现出更为严重糖耐量受损（P <0. 01）、脂质代谢紊乱（P <0. 01）、血清胆汁酸增高（P <0. 01）、肝脏炎症（P <0. 01）和肝脏脂肪变性。结论 FXR的缺失引起小鼠糖脂代谢紊乱、胆汁酸代谢异常、肝脏脂肪变性,但这种改变需要高脂饮食的诱导。

Effect of High Fat Diet on Glycolipid Metabolism and Hepatic Steatosis in Farnesoid X Receptor (FXR) Knockout Mice

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.