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

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11 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)7788-7803
頁數16
期刊Oncotarget
6
發行號10
出版狀態已發佈 - 2015

ASJC Scopus subject areas

  • 腫瘤科

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