title: Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC-1α-dependent pathway.
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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hong-Jhih
authors.initials: HJ
authors.lastname: Jhuang
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Hsiang
authors.initials: WH
authors.lastname: Hsu
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chiayi, Taiwan.
authors.forename: Feng-Sheng
authors.initials: FS
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chen-Kung
authors.initials: CK
authors.lastname: Chou
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kuen-Haur
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ann-Ping
authors.initials: AP
authors.lastname: Tsou
authors.affiliation: Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Lai
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Sheau-Farn
authors.initials: SF
authors.lastname: Yeh
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.|Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.|Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chi-Ying F
authors.initials: CY
authors.lastname: Huang
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor; D029627:Crassulaceae / Q000737:chemistry; D004261:DNA Replication / Q000502:physiology*; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005943:Gluconeogenesis; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D050155:Lipogenesis; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010936:Plant Extracts; D014157:Transcription Factors; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003907:Dexamethasone
keywords: Graptopetalum paraguayense; HBV; PGC-1α; gluconeogenesis; lipogenesis