Oncotarget

Research Papers:

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

Hong-Jhih Jhuang _, Wei-Hsiang Hsu, Kuan-Ting Lin, Shih-Lan Hsu, Feng-Sheng Wang, Chen-Kung Chou, Kuen-Haur Lee, Ann-Ping Tsou, Jin-Mei Lai, Sheau-Farn Yeh and Chi-Ying F. Huang

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Oncotarget. 2015; 6:7788-7803. https://doi.org/10.18632/oncotarget.3050

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Abstract

Hong-Jhih Jhuang1,*, Wei-Hsiang Hsu2,*, Kuan-Ting Lin3, Shih-Lan Hsu4, Feng-Sheng Wang5, Chen-Kung Chou6, Kuen-Haur Lee8, Ann-Ping Tsou9, Jin-Mei Lai7, Sheau-Farn Yeh1, Chi-Ying F. Huang2,3,9

1Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan

2Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan

3Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan

4Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan

5Department of Chemical Engineering, National Chung Cheng University, Chiayi, Taiwan

6Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan

7Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan

8Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

9Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Jin-Mei Lai, e-mail: jmlai@mail.fju.edu.tw

Sheau-Farn Yeh, e-mail: fyeh@ym.edu.tw

Chi-Ying F. Huang, e-mail: cyhuang5@ym.edu.tw

Keywords: Graptopetalum paraguayense, HBV, Gluconeogenesis, Lipogenesis, PGC-1α

Received: November 04, 2014     Accepted: January 06, 2015     Published: February 03, 2015

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.


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