Changes in the expression of cholesterol metabolism-associated genes in HCV-infected liver: A novel target for therapy?

Makoto Nakamuta, Ryoko Yada, Tatsuya Fujino, Masayoshi Yada, Nobito Higuchi, Masatake Tanaka, Masayuki Miyazaki, Motoyuki Kohjima, Masaki Kato, Tsuyoshi Yoshimoto, Naohiko Harada, Akinobu Taketomi, Yoshihiko Maehara, Momoko Koga, Takuya Nishinakagawa, Manabu Nakashima, Kazuhiro Kotoh, Munechika Enjoji

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Recent investigations indicate that hepatitis C virus (HCV) infection is closely associated with hepatocytic lipid metabolism and induces hepatic steatosis. However, the actual lipid metabolism in HCV-infected liver has not been extensively investigated in humans. In this study, we evaluated the expression of lipid metabolism-associated genes in patients with HCV infection by real-time PCR. Sterol regulatory element-binding protein (SREBP)-2 expression was unchanged and low density lipoprotein receptor expression was markedly reduced by 90% in HCV-infected liver. The expression of apolipoprotein B100, microsomal triglyceride transfer ptotein and ATP-binding cassette G5 was significantly increased. Up-regulation of cholesterol synthesis-associated genes, including HMG-CoA reductase, HMG-CoA synthase, farnesyl-diphosphate synthase and squalene synthase, confirmed enhanced de novo cholesterol synthesis. The expression of cholesterol 7α-hydroxylase and farnesoid X receptor was enhanced, while bile salt export pump expression was unchanged. Fatty acid synthase expression was increased which was accompanied by increased expression of liver X receptor α and SREBP-1c. In summary, the regulation of lipid metabolism was impaired and cholesterol and fatty acid synthesis continued to increase without negative feedback in HCV-infected liver. These changes may be beneficial for HCV replication.

Original languageEnglish
Pages (from-to)825-828
Number of pages4
JournalInternational journal of molecular medicine
Volume24
Issue number6
DOIs
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • Genetics

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