Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway.
The population of hepatitis B combined with a number of metabolic disorders is increasing significantly. Resveratrol (RSV) has been used as a preclinical drug for the treatment of the metabolic disorders. However, the impact of RSV on HBV replication remains unknown. In this study, the HBV-expressing hepatocelluar carcinoma cell line and mouse model created by hydrodynamic injection of viral DNA were used. We found that RSV activates Sirt1, which in turn deacetylates PGC-1α and subsequently increases the transcriptional activity of PPARα, leading to the enhanced HBV transcription and replication in vitro and in vivo. In addition, we found that this pathway is also required for fasting-induced HBV transcription. Taken together, this study identifies that RSV enhances HBV transcription and replication especially acting on the core promoter, which depends on Sirt1-PGC-1α-PPARα pathway. We conclude that RSV may exacerbate the progression of hepatitis B and that patients with hepatitis B infection should be cautious taking RSV as a dietary supplement.
State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Yixian
Y
Shi
State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Yongjun
Y
Li
State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Chenjie
C
Huang
Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Lixiong
L
Ying
Department of Infectious Disease, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
Jihua
J
Xue
Department of Hepatobiliary Medicine, Fuzhou General Hospital of Nanjing Military Command, Fuzhou 350025, Fujian, China.
Haicong
H
Wu
State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Zhi
Z
Chen
State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Zhenggang
Z
Yang
D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000378:metabolism* / Q000821:virology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D006801:Humans; D051379:Mice; D047493:PPAR alpha / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D013267:Stilbenes; D056564:Sirtuin 1; D000077185:Resveratrol