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Hepatitis B virus X protein induces hepatic steatosis by enhancing the expression of liver fatty acid binding protein
Author(s) -
Lin Xu,
Wu YunLi,
Peng XianE,
Zhu YiBing,
Yan XiaoLi,
Chen WanNan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.870.1
Subject(s) - hbx , steatosis , gene knockdown , chromatin immunoprecipitation , fatty liver , hepatitis b virus , biology , ectopic expression , microbiology and biotechnology , chemistry , endocrinology , medicine , gene expression , biochemistry , virology , gene , virus , promoter , disease
BACKGROUND & AIMS Hepatitis B virus (HBV) has been implicated as a potential trigger of hepatic steatosis although the molecular mechanism involved in the pathogenesis of HBV‐associated hepatic steatosis still remains elusive. Our prior work has revealed that the expression level of liver fatty acid binding protein (FABP1), a key regulator of hepatic lipid metabolism, was elevated in HBV‐producing hepatoma cells. In this study, we sought to determine the effects of Hepatitis B X protein (HBx)‐mediated FABP1 regulation on hepatic steatosis and the underlying mechanism. METHODS mRNA and protein level of FABP1 were measured by quantitative RT‐PCR and western blot. HBx‐mediated FABP1 regulation was evaluated by luciferase assay, co‐immunoprecipitation and chromatin immunoprecipitation. Hepatic lipid accumulation was measured by Oil‐Red‐O staining and triglyceride level. RESULTS Expression of FABP1 was dramatically increased in HBV‐producing hepatoma cells, serum of HBV‐infected patients, and serum and liver tissues of HBV‐transgenic mice. Ectopic overexpression of HBx resulted in up‐regulation of FABP1 in HBx‐expressing hepatoma cells whereas HBx abolishment reduced FABP1 expression. Mechanistically, HBx activated FABP1 promoter in HNF3β, C/EBPα and PPARα‐dependent manner, in which HBx increased the expression of HNF3β and physically interacted with C/EBPα and PPARα. On the other way around, knockdown of FABP1 remarkably blocked lipid accumulation both in long‐chain fatty acids treated HBx‐expressing HepG2 cells and in a high fat diet fed HBx‐transgenic mice. CONCLUSIONS FABP1 is a key driver gene in HBx‐induced hepatic lipid accumulation via regulation of HNF3β, C/EBPα and PPARα. FABP1 may represent a novel target for treatment of HBV‐associated hepatic steatosis. Support or Funding Information This work was supported by the grants from National Natural Science Foundation of China (Grant number 81271822 and 81401657), State Key Project Specialized for Infectious Diseases (2012ZX10002002‐004‐006 and 2013ZX10002002‐005‐002) and Foundation of Fujian Educational Committee (Grant number JK2013021).