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Pathogenesis of lipid metabolism disorder in hepatitis C: polyunsaturated fatty acids counteract lipid alterations induced by the core protein.

Authors :
Miyoshi H
Moriya K
Tsutsumi T
Shinzawa S
Fujie H
Shintani Y
Fujinaga H
Goto K
Todoroki T
Suzuki T
Miyamura T
Matsuura Y
Yotsuyanagi H
Koike K
Source :
Journal of hepatology [J Hepatol] 2011 Mar; Vol. 54 (3), pp. 432-8. Date of Electronic Publication: 2010 Sep 22.
Publication Year :
2011

Abstract

Background & Aims: 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.<br />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.<br />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.<br />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.<br /> (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1600-0641
Volume :
54
Issue :
3
Database :
MEDLINE
Journal :
Journal of hepatology
Publication Type :
Academic Journal
Accession number :
21093950
Full Text :
https://doi.org/10.1016/j.jhep.2010.07.039