Changes in the expression of cholesterol metabolism-associated genes in HCV-infected liver: a novel target for therapy?
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.
Nakamuta
Makoto
M
Clinical Research Center, National Hospital Organization, Fukuoka, Japan.
Yada
Ryoko
R
Fujino
Tatsuya
T
Yada
Masayoshi
M
Higuchi
Nobito
N
Tanaka
Masatake
M
Miyazaki
Masayuki
M
Kohjima
Motoyuki
M
Kato
Masaki
M
Yoshimoto
Tsuyoshi
T
Harada
Naohiko
N
Taketomi
Akinobu
A
Maehara
Yoshihiko
Y
Koga
Momoko
M
Nishinakagawa
Takuya
T
Nakashima
Manabu
M
Kotoh
Kazuhiro
K
Enjoji
Munechika
M
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
D002784:Cholesterol