HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPARgamma.
Hepatic steatosis is a common feature in patients with chronic hepatitis C virus (HCV) infection. HCV core protein plays an important role in the development of hepatic steatosis in HCV infection. Because SREBP1 (sterol regulatory element binding protein 1) and PPARgamma (peroxisome proliferators-activated receptor gamma) are involved in the regulation of lipid metabolism of hepatocyte, we sought to determine whether HCV core protein may impair the expression and activity of SREBP1 and PPARgamma. In this study, it was demonstrated that HCV core protein increases the gene expression of SREBP1 not only in Chang liver, Huh7, and HepG2 cells transiently transfected with HCV core protein expression plasmid, but also in Chang liver-core stable cells. Furthermore, HCV core protein enhanced the transcriptional activity of SREBP1. In addition, HCV core protein elevated PPARgamma transcriptional activity. However, HCV core protein had no effect on PPARgamma gene expression. Finally, we showed that HCV core protein stimulates the genes expression of lipogenic enzyme and fatty acid uptake associated protein. Therefore, our finding provides a new insight into the mechanism of hepatic steatosis by HCV infection.
Kim
Kook Hwan
KH
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
Hong
Sung Pyo
SP
Kim
Kyeongjin
K
Park
Min Jung
MJ
Kim
Kwang Jin
KJ
Cheong
Jaehun
J
D002460:Cell Line; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
D005227:Fatty Acids; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D014758:Viral Core Proteins