The role of Hepatocyte nuclear factor 4 alpha in the non-alcoholic fatty liver disease

Abstract

The hepatic HNF4α expression was significantly increased in both the NAFLD and NASH subjects as compared to the control subjects. Hepatic expression of bile acid metabolism genes was showing greater expression in NAFLD groups. The protein expression of hepatic HNF4α increased significantly in HF and MCD diet induced NAFLD models. As compared to the control, hepatic mRNA expression of SHP and NTCP decreased significantly, while Cyp7A1 increased, although not significantly in both the HF and MCD diet induced NAFLD models. HNF4α over-expression of HNF4α increased the mRNA expressions of CPT1A, ACOX1 and ApoB; however, FAS, SCD-1, CD36 and FATP2 expressions were unaffected. Furthermore, HNF4α over-expression decreased PA induced cell viability and OA induced triglyceride contents in HepG2 cells. HNF4α down-regulation had no effect on palmatic acid induced cell proliferation. HNF4α overexpression had no significant effect on bile acid toxicity. In addition, HNF4α over-expression did not increase of apoptotic cells by palmitic acid and CDCA co-treatment, the Cyp7A1, Cyp8B1 and NTCP mRNA expressions increased 60-folds in HNF4α over-expression groups as compared to controls. The HNF4α over-expression increased hepatic apoptosis, which may be account for Cyp7A1, Cyp8bB1 and NTCP expression in PA and CDCA combine treatment. The HNF4α down-regulation significant attenuated palmatic acid and CDCA co-treatment induced growth inhibition. In addition, HNF4α siRNA did decrease of apoptotic cells by palmatic acid and CDCA co-tratment. HNF4α siRNA did decrease the expression of Cyp7A1, Cyp8B1 and NTCP. Notably, HNF4α plays a different role in apoptosis of lipotoxicity model and bile acid toxicity model. Hepatic HNF4α is indispensable for maintaining normal lipid homeostasis and bile acid homeostasis and it might be a potential therapeutic target of NAFLD.