Hepatitis C virus core protein modulates fatty acid metabolism and thereby causes lipid accumulation in the liver.
We studied the roles of hepatitis C virus (HCV) core protein in hepatic steatosis and changes in hepatic lipid metabolism. HCV core protein expression plasmid was transfected in HepG2. Triacylglyceride (TG) and mRNA level associated with lipid metabolism were measured. Male C57BL/6 mice were infected with HCV core recombinant adenovirus and used for lipids and mRNA studies. In HCV core protein-expressing cells, peroxisome proliferator-activated receptor (PPAR)alpha, multidrug resistance protein (MDR) 3, and microsomal triglyceride transfer protein (MTP) were down-regulated 48 hr after transfection. In HCV core protein-expressing mice, hepatic TG content and hepatic thiobarbituric acid-reactive substances increased. PPARalpha, MDR2, acyl-CoA oxidase (AOX), and carnitine palmitoyl transferase-1 (CPT-1) were down-regulated. HCV core protein down-regulated lipid metabolism-associated gene expression, Mdr2, CPT, and AOX, accompanied by down-regulation of PPARalpha. There findings may contribute to the understanding of HCV-related steatosis, induction of reactive oxygen species, and carcinogenesis.
Yamaguchi
Atsushi
A
Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Tazuma
Susumu
S
Nishioka
Tomoji
T
Ohishi
Waka
W
Hyogo
Hideyuki
H
Nomura
Shuichi
S
Chayama
Kazuaki
K
D000818:Animals; D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism / Q000502:physiology*
D005227:Fatty Acids; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus