Enhancement of de Novo Fatty Acid Biosynthesis in Hepatic Cell Line Huh? Expressing Hepatitis C Virus Core Protein

• Published in: Biological & Pharmaceutical Bulletin 2006, Vol.29 (9), p.1958-1961
• Main Authors: Masayoshi FUKASAWAa, Yasuhito TANAKAa, Shigeko SATOa, Yujin ONOa, Yuko NITAHARA-KASAHARAa, Tetsuro SUZUKIb, Tatsuo MIYAMURAb, Kentaro HANADAa, Masahiro NISHIJIMAa, c
• Format: Article
• Language: Japanese
• ISSN: 0918-6158

Hepatitis C virus (HCV) core protein plays important roles in the pathogeneses of liver steatosis as well as hepatocellular carcinomas due to HCV infection. In this study, we examined de novo fatty acid biosynthesis in hepatic cell line Huh7 cells expressing HCV core protein. The rate of metabolic labeling of cellular fatty acids with [3H]acetate in core-expressing (Uc39-6) cells was ca. 1. 5-fold higher than that in non-expressing (Uc321) cells. The enzyme activities responsible for fatty acid biosynthesis were assayed in vitro. Cytosolic acetyl-CoA carboxylase activity in Uc39-6 cells was ca. 1.6-fold higher than that in Uc321 cells. On the other hand, cytosolic fatty acid synthase activity in Uc39-6 cells was only slightly higher than that in Uc321 cells. Immunoblot analysis of acetyl-CoA carboxylase 1 (ACC1), which is a rate-limiting enzyme for fatty acid biosynthesis, revealed a higher expression level of the protein in Uc39-6 cells than in Uc321 cells. The ACC1 mRNA content in Uc39-6 cells was 1.4-fold higher than that in Uc321 cells. These results strongly suggest that enhancement of fatty acid biosynthesis in core-expressing cells is caused by increased expression of fatty acid biosynthetic enzymes, especially AM. Up-regulation of de novo fatty acid biosynthesis by HCV core protein may affect cellular lipid metabolism, resulting in neutral lipid accumulation in HCV infected cells.