Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARγ

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Title
Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARγ
Author(s)
K H Kim; Hye Jun Shin; K Kim; H M Choi; S H Rhee; H Moon; H H Kim; U S Yang; Dae Yeul Yu; J Cheong
Bibliographic Citation
Gastroenterology, vol. 132, no. 5, pp. 1955-1967
Publication Year
2007
Abstract
Background & Aims: 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 (PPARα). Moreover, we also determined that the expression of HBx increases PPARγ gene expression as well as its transcriptional activity in hepatic cells, mediated by CCAAT enhancer binding protein α 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 PPARγ, which could be a putative molecular mechanism mediating the pathophysiology of HBV infection.
ISSN
0016-5085
Publisher
Elsevier
DOI
http://dx.doi.org/10.1053/j.gastro.2007.03.039
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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