Browse

Liver X Receptor Mediates Hepatitis B Virus X Protein-Induced Lipogenesis in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Cited 105 time in Web of Science Cited 107 time in Scopus
Authors
Na, Tae-Young; Shin, Young Kee; Kang, Shin-Ae; Roh, Kyung Jin; Seong, Je Kyung; Choi, Yoon La; Lee, Mi-Ock; Park, Cheol Keun; Oh, Sae Jin; Hong, Il
Issue Date
2009-04
Publisher
JOHN WILEY & SONS INC
Citation
HEPATOLOGY; Vol.49, No.4, pp.1122-1131
Description
The definitive version is available at www3.interscience.wiley.com
Abstract
Although hepatitis B virus X protein (HBx) has been implicated in abnormal lipid metabolism in hepatitis B virus (HBV)-associated hepatic steatosis, its underlying molecular mechanism remains unclear. Liver X receptor (LXR) plays an important role in regulating the expression of genes involved in hepatic lipogenesis. Here we demonstrate that LXR alpha and LXR beta mediate HBV-associated hepatic steatosis. We have found that HBx induces the expression of LXR and its lipogenic target genes, such as sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor, and this is accompanied by the accumulation of lipid droplets. RNA interference with LXR expression decreases the amount of lipid droplets as well as the expression of the lipogenic genes, and this indicates that HBx-induced lipogenesis is LXR-dependent. LXR alpha and HBx colocalize in the nucleus and are physically associated. HBx induces the transactivation function of LXR alpha by recruiting CREB binding protein to the promoter of the target gene. Furthermore, we have observed that expression of LXR is increased in the livers of HBx-transgenic mice. Finally, there is a significant increase in the expression of LXR beta (P = 0.036), SREBP-1c (P = 0.008), FAS, and stearoyl-coenyzme A desaturase-1 (P = 0.001) in hepatocellular carcinoma (HCC) in comparison with adjacent nontumorous nodules in human HBV-associated HCC specimens. Conclusion: Our results suggest a novel association between HBx and LXR that may represent an important mechanism explaining HBx-induced hepatic lipogenesis during HBV-associated hepatic carcinogenesis. (HEPATOLOGY 2009; 49:1122-1131.)
ISSN
0270-9139
Language
English
URI
http://hdl.handle.net/10371/80933
DOI
https://doi.org/10.1002/hep.22740
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse