Format

Send to

Choose Destination
Oncotarget. 2015 Apr 10;6(10):7788-803.

Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC-1α-dependent pathway.

Author information

1
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
2
Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
3
Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
4
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
5
Department of Chemical Engineering, National Chung Cheng University, Chiayi, Taiwan.
6
Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
7
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
8
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
9
Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan.

Abstract

PGC-1α, a major metabolic regulator of gluconeogenesis and lipogenesis, is strongly induced to coactivate Hepatitis B virus (HBV) gene expression in the liver of fasting mice. We found that 8-Br-cAMP and glucocorticoids synergistically induce PGC-1α and its downstream targets, including PEPCK and G6Pase. Also, HBV core promoter activity was synergistically enhanced by 8-Br-cAMP and glucocorticoids. Graptopetalum paraguayense (GP), a herbal medicine, is commonly used in Taiwan to treat liver disorders. Partially purified fraction of GP (named HH-F3) suppressed 8-Br-cAMP/glucocorticoid-induced G6Pase, PEPCK and PGC-1α expression and suppressed HBV core promoter activity. HH-F3 blocked HBV core promoter activity via inhibition of PGC-1α expression. Ectopically expressed PGC-1α rescued HH-F3-inhibited HBV surface antigen expression, HBV mRNA production, core protein levels, and HBV replication. HH-F3 also inhibited fatty acid synthase (FASN) expression and decreased lipid accumulation by down-regulating PGC-1α. Thus, HH-F3 can inhibit HBV replication, gluconeogenesis and lipogenesis by down-regulating PGC-1α. Our study indicates that targeting PGC-1α may be a therapeutic strategy for treatment of HBV infections. HH-F3 may have potential use for the treatment of chronic hepatitis B patients with associated metabolic syndrome.

KEYWORDS:

Graptopetalum paraguayense; HBV; PGC-1α; gluconeogenesis; lipogenesis

PMID:
25762623
PMCID:
PMC4480716
DOI:
10.18632/oncotarget.3050
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center