Lipid metabolism and liver disease in hepatitis C viral infection.
Persistent infection with hepatitis C virus (HCV) is a major risk toward development of hepatocellular carcinoma. A number of transgenic mouse lines carrying the cDNA of HCV genome have been established and evaluated in the study of HCV pathogenesis. Among those, the studies using transgenic mouse lines that carry the HCV genome containing the core gene indicate the direct involvement of HCV in pathogenicity, including that in oncogenesis. Oxidative stress overproduction and intracellular signaling augmentation are shown to be the key events in HCV-associated hepatocarcinogenesis. Besides the data in hepatitis C patients, connecting liver fibrosis progression and the disturbance in lipid and glucose metabolisms, these mouse models also show a close relationship between HCV and metabolic alterations including hepatic steatosis and insulin resistance. Furthermore, the persistent activation of peroxisome proliferator-activated receptor-alpha has recently been found, yielding dramatic changes in the lipid metabolism and oxidative stress overproduction in cooperation with the mitochondrial dysfunction. These results would provide a clue for further understanding of the role of lipid metabolism in pathogenesis of hepatitis C including liver injury and hepatocarcinogenesis.
Koike
Kazuhiko
K
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. kkoike-tky @ umin.ac.jp
Tsutsumi
Takeya
T
Yotsuyanagi
Hiroshi
H
Moriya
Kyoji
K
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000378:metabolism* / Q000821:virology; D006801:Humans; D050356:Lipid Metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology; D051379:Mice; D018384:Oxidative Stress; D015398:Signal Transduction