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, Chi Ying F Huang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

PGC-1a, 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.

Original languageEnglish
Pages (from-to)7788-7803
Number of pages16
JournalOncotarget
Volume6
Issue number10
Publication statusPublished - 2015

Keywords

  • Gluconeogenesis
  • Graptopetalum paraguayense
  • HBV
  • Lipogenesis
  • PGC-1α

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Jhuang, H. J., Hsu, W. H., Lin, K. T., Hsu, S. L., Wang, F. S., Chou, C. K., Lee, K. H., Tsou, A. P., Lai, J. M., Yeh, S. F., & Huang, C. Y. F. (2015). Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC-1α-dependent pathway. Oncotarget, 6(10), 7788-7803.