title: Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARgamma.
abstract: OBJECTIVE
  Hepatic steatosis occurs frequently in patients with chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection. Recently, several studies suggested that steatosis plays an important role as a cofactor in other liver diseases such as hepatic fibrosis, hepatitis, and liver cancer. In contrast to HCV, however, the molecular mechanism by which HBV mediates hepatic steatosis has not been clearly studied. Here, we show the molecular mechanism by which hepatitis B virus X protein (HBx) induces hepatic steatosis.
  
  
  METHODS
  Lipid accumulation and the expression of various lipid metabolic genes were investigated in HBx-transfected Chang liver cells, HepG2-HBx stable cells, and HBx-transgenic mice.
  
  
  RESULTS
  Overexpression of HBx induced hepatic lipid accumulation in HepG2-HBx stable cells and HBx-transgenic mice. It also up-regulated the messenger RNA and protein levels of sterol regulatory element binding protein 1, but not peroxisome proliferator-activated receptor alpha (PPARalpha). Moreover, we also determined that the expression of HBx increases PPARgamma gene expression as well as its transcriptional activity in hepatic cells, mediated by CCAAT enhancer binding protein alpha activation. Finally, we showed that HBx expression is able to up-regulate the gene expressions of various lipogenic and adipogenic enzymes in hepatic cells.
  
  
  CONCLUSIONS
  We showed that the increased HBx expression causes lipid accumulation in hepatic cells mediated by sterol regulatory element binding protein 1 and PPARgamma, which could be a putative molecular mechanism mediating the pathophysiology of HBV infection.
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan, Korea.
authors.forename: Kook Hwan
authors.initials: KH
authors.lastname: Kim
authors.forename: Hye-Jun
authors.initials: HJ
authors.lastname: Shin
authors.forename: Kyeongjin
authors.initials: K
authors.lastname: Kim
authors.forename: Hyun Mi
authors.initials: HM
authors.lastname: Choi
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Rhee
authors.forename: Hyung-Bae
authors.initials: HB
authors.lastname: Moon
authors.forename: Hyeong Hoe
authors.initials: HH
authors.lastname: Kim
authors.forename: Ung Suk
authors.initials: US
authors.lastname: Yang
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
authors.forename: Jaehun
authors.initials: J
authors.lastname: Cheong
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000502:physiology; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D005234:Fatty Liver / Q000235:genetics / Q000503:physiopathology* / Q000821:virology*; D005786:Gene Expression Regulation; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D000103:Acetyl-CoA Carboxylase; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D013230:Stearoyl-CoA Desaturase; D051780:Sterol Regulatory Element Binding Protein 1; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C497388:Srebf1 protein, mouse; C057628:hepatitis B virus X protein