title: Changes in the expression of cholesterol metabolism-associated genes in HCV-infected liver: a novel target for therapy?
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 protein 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 7alpha-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 alpha 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.
authors.affiliation: Clinical Research Center, National Hospital Organization, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujino
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yada
authors.forename: Nobito
authors.initials: N
authors.lastname: Higuchi
authors.forename: Masatake
authors.initials: M
authors.lastname: Tanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Naohiko
authors.initials: N
authors.lastname: Harada
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Momoko
authors.initials: M
authors.lastname: Koga
authors.forename: Takuya
authors.initials: T
authors.lastname: Nishinakagawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakashima
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
mesh_terms: D000368:Aged; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002784:Cholesterol