title: Pathogenesis of lipid metabolism disorder in hepatitis C: polyunsaturated fatty acids counteract lipid alterations induced by the core protein.
abstract: OBJECTIVE
  Disturbance in lipid metabolism is one of the features of chronic hepatitis C, being a crucial determinant of the progression of liver fibrosis. Experimental studies have revealed that the core protein of hepatitis C virus (HCV) induces steatosis.
  
  
  METHODS
  The activities of fatty acid metabolizing enzymes were determined by analyzing the fatty acid compositions in HepG2 cells with or without core protein expression.
  
  
  RESULTS
  There was a marked accumulation of triglycerides in core-expressing HepG2 cells. While the oleic/stearic acid (18:1/18:0) and palmitoleic/palmitic acid ratio (16:1/16:0) were comparable in both the core-expressing and the control cells, there was a marked accumulation of downstream product, 5,8,11-eicosatrienoic acid (20:3(n-9)) in the core-expressing HepG2 cells. The addition of eicosatetraynoic acid, which inhibits delta-6 desaturase activity which is inherently high in HepG2 cells, led to a marked accumulation of oleic and palmitoleic acids in the core-expressing cells, showing that delta-9 desaturase was activated by the core protein. Eicosapentaenoic acid (20:5(n-3)) or arachidonic acid (20:4(n-6)) administration significantly decreased delta-9 desaturase activity, the concentration of 20:3(n-9), and triglyceride accumulation. This lipid metabolism disorder was associated with NADH accumulation due to mitochondrial dysfunction, and was reversed by the addition of pyruvate through NADH utilization.
  
  
  CONCLUSIONS
  The fatty acid enzyme, delta-9 desaturase, was activated by HCV core protein and polyunsaturated fatty acids counteracted this impact of the core protein on lipid metabolism. These results may open up new insights into the mechanism of lipid metabolism disorder associated with HCV infection and provide clues for the development of new therapeutic devices.
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Kyoji
authors.initials: K
authors.lastname: Moriya
authors.forename: Takeya
authors.initials: T
authors.lastname: Tsutsumi
authors.forename: Seiko
authors.initials: S
authors.lastname: Shinzawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujie
authors.forename: Yoshizumi
authors.initials: Y
authors.lastname: Shintani
authors.forename: Hidetake
authors.initials: H
authors.lastname: Fujinaga
authors.forename: Koji
authors.initials: K
authors.lastname: Goto
authors.forename: Toru
authors.initials: T
authors.lastname: Todoroki
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Miyamura
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yotsuyanagi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism*; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000378:metabolism* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism; D052439:Lipid Metabolism Disorders / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D005231:Fatty Acids, Unsaturated; D007657:Ketone Bodies; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D014758:Viral Core Proteins; D013230:Stearoyl-CoA Desaturase