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Hepatitis C Virus Core Protein Modulates Fatty Acid Metabolism and Thereby Causes Lipid Accumulation in the Liver

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Abstract

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)α, 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. PPARα, 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 PPARα. There findings may contribute to the understanding of HCV-related steatosis, induction of reactive oxygen species, and carcinogenesis.

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    PubMed  Google Scholar 

  46. Rubbia-Brandt L, Quadri R, Abid K, Giostra E, Male PJ, Mentha G, Spahr L, Zarski JP, Borisch B, Hadengue A, Negro F: Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol 33:106–115, 2000

    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    PubMed  Google Scholar 

  50. Barba G, Harper F, Harada T, Kohara M, Goulinet S, Matsuura Y, Eder G, Schaff Z, Chapman MJ, Miyamura T, Brechot C: Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc Natl Acad Sci USA 94:1200–1205, 1997

    PubMed  Google Scholar 

  51. Ray RB, Lagging LM, Meyer K, Ray R: Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype. J Virol 70:4438–4443, 1996

    PubMed  Google Scholar 

  52. Ray RB, Meyer K, Ray R: Suppression of apoptotic cell death by hepatitis C virus core protein. Virology 226:176–182, 1996

    PubMed  Google Scholar 

  53. Zhu N, Khoshnan A, Schneider R, Matsumoto M, Dennert G, Ware C, Lai MM: Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis. J Virol 72:3691–3697, 1998

    PubMed  Google Scholar 

  54. Honda M, Kaneko S, Shimazaki T, Matsushita E, Kobayashi K, Ping LH, Zhang HC, Lemon SM: Hepatitis C virus core protein induces apoptosis and impairs cell-cycle regulation in stably transformed Chinese hamster ovary cells. Hepatology 31:1351–1359, 2000

    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    PubMed  Google Scholar 

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    Google Scholar 

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    PubMed  Google Scholar 

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    Google Scholar 

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    PubMed  Google Scholar 

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    Google Scholar 

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    PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

    Atsushi Yamaguchi MD, Tomoji Nishioka MD, PhD, Waka Ohishi MD, PhD & Kazuaki Chayama MD, PhD

  2. Departments of General Medicine and Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

    Susumu Tazuma MD, PhD, Hideyuki Hyogo MD, PhD & Shuichi Nomura MD, PhD

  3. Department of General Medicine and Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Susumu Tazuma MD, PhD

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  1. Atsushi Yamaguchi MD
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  2. Susumu Tazuma MD, PhD
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  3. Tomoji Nishioka MD, PhD
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Correspondence to Susumu Tazuma MD, PhD.

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Yamaguchi, A., Tazuma, S., Nishioka, T. et al. Hepatitis C Virus Core Protein Modulates Fatty Acid Metabolism and Thereby Causes Lipid Accumulation in the Liver. Dig Dis Sci 50, 1361–1371 (2005). https://doi.org/10.1007/s10620-005-2788-1

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