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Hepatitis C as a Metabolic Disease : Pathogenesis for liver cancer and lifestyle-related diseases

Research Project

Project/Area Number 18390214
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

KOIKE Kazuhiko  The University of Tokyo, Graduate School of Medicine, Professor (80240703)

Co-Investigator(Kenkyū-buntansha) FUJIE Hajime  University of Tokyo, Faculty of Medicine, Associate (90332577)
YOTSUYANAGI Hiroshi  University of Tokyo, Faculty of Medicine, Hospital, Lecturer (30251234)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥17,400,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2006: ¥9,600,000 (Direct Cost: ¥9,600,000)
KeywordsHCV / insulin resistance / steatosis / transgenic mouse / metabolism / proteasome activator / nuclear receptor / プロテアゾームアクテベーター / プロテアゾームアクチベーター
Research Abstract

In addition to the link with development of hepatocellular carcinoma (HCC), hepatitis C virus (HCV) infection is associated with several hepatic and extrahepatic manifestations. A role of hepatic steatosis in the pathogenesis of chronic hepatitis C has been shown, implying hepatitis C as a metabolic disease. Furthermore, recent epidemiological studies have suggested a linkage between insulin resistance and chronic HCV infection. Besides the data indicating the presence of lipid metabolism disturbance and insulin resistance in the cohort of chronic hepatitis C patients, we found a series of evidence showing the association between these two conditions and HCV infection using mice transgenic for the HCV core gene. These mice develop HCC late in life after the phase of hepatic steatosis and insulin resistance. The nonappearance of both steatosis and HCC in HCV core gene transgenic mice that are null for the proteasome activator 28g, implies a close relationship between lipid metabolism disturbance and hepatocarcinogenesis. Also, the core protein is shown to bind with retinoid X receptor (RXR)-a, resulting in the up-regulation of some lipid metabolism enzymes including cellular retinol binding protein II and acyl-CoA oxidase. In addition, the persistent activation of peroxisome proliferator activated receptor (PPAR)-a has recently been found in the liver of HCV core gene transgenic mice, yielding dramatic changes in the lipid metabolism and hepatocyte proliferation including HCC development. These results would provide a clue for further understanding of the role of lipid metabolism in pathogenesis of HCV infection including liver injury and hepatocarcinogenesis.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (19 results)

All 2008 2007 2006

All Journal Article (13 results) (of which Peer Reviewed: 5 results) Presentation (3 results) Book (3 results)

  • [Journal Article] PPAR-alpha is essential for severe hepatic steatosis and hepatocellular carcinoma induced by HCV core protein.2008

    • Author(s)
      Tanaka N, et. al.
    • Journal Title

      J. Clin Invest 118

      Pages: 683-694

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] PPAR-alpha is essential for severe hepatic steatosis and hepatocellular carcinoma induced by HCV core protein2008

    • Author(s)
      Tanaka N, et. al.
    • Journal Title

      J Clin Invest 118

      Pages: 683-694

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] PPAR-alpha is essntial for severe hepatic steatosis and hepatocellular carcinoma induced by HCV core protein2008

    • Author(s)
      Tanaka N, et. al.
    • Journal Title

      J Chin Invest 118

      Pages: 683-694

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of PA28γ in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis2007

    • Author(s)
      Moriishi K, et. al.
    • Journal Title

      Proc Natl Acad Sci USA 104

      Pages: 1661-1666

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hepatitis C Virus Core Protein Induces Insulin Resistance through a PA28Y-Dependent Pathway2007

    • Author(s)
      Miyamoto H, et. al.
    • Journal Title

      J. Virol 81

      Pages: 1727-1735

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hepatitis C Virus Core Protein Induces Insulin Resistance through a PA28γ-Dependent Pathway2007

    • Author(s)
      Miyamoto H, et. al.
    • Journal Title

      J Virol 81

      Pages: 1727-1735

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Journal Article] Critical role of PA28γ in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis2007

    • Author(s)
      Morhshi K, et. al.
    • Journal Title

      Proc Natl Acad Sci USA 104

      Pages: 1661-1666

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of PA28γ in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis.2007

    • Author(s)
      Moriishi K, et al.
    • Journal Title

      Proc Natl Acad Sci USA 104

      Pages: 1661-1666

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hepatitis C Virus Core Protein Induces Insulin Resistance through a PA28γ-Dependent Pathway2007

    • Author(s)
      Miyamoto H, et al.
    • Journal Title

      J Virol 81

      Pages: 1727-1735

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus2007

    • Author(s)
      Suzuki Y, et al.
    • Journal Title

      World J Gastroenterol 13

      Pages: 964-969

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hepatitis C virus infection presenting with metabolic disease by inducing insulin resistance2006

    • Author(s)
      Koike K.
    • Journal Title

      Intervirology 19

      Pages: 51-57

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Antiviral treatment of hepatitis C : present status and future prospects2006

    • Author(s)
      Koike K.
    • Journal Title

      J Infect Chemother 12

      Pages: 227-232

    • NAID

      10018347988

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oxidative stress and hepatitis C viral infection2006

    • Author(s)
      Koike K, Miyoshi H
    • Journal Title

      Hepatol Res 34

      Pages: 65-76

    • NAID

      10020405552

    • Related Report
      2006 Annual Research Report
  • [Presentation] FK506 ameliorates metabolic disturbance and oxidative stress in hepatitis C virus infection2007

    • Author(s)
      Moriya K, et. al.
    • Organizer
      42nd Annual Meeting of the EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER
    • Place of Presentation
      スペイン(バルセロナ)
    • Year and Date
      2007-04-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] FK506 ameliorates metabolic disturbance and oxidative stress in hepatitis C virus infection2007

    • Author(s)
      Moriya K, et. al.
    • Organizer
      42nd Annual Meeting of the EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER
    • Place of Presentation
      Barcelona
    • Year and Date
      2007-04-24
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] FK506 ameliorates metabolic disturbance and oxidative stress in hepatitis C virus infection2007

    • Author(s)
      Moriya K, et. al.
    • Organizer
      42ndAnnual Meeting of the EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER
    • Place of Presentation
      スペイン(バルセロナ)
    • Year and Date
      2007-04-24
    • Related Report
      2007 Annual Research Report
  • [Book] 肝癌診療マニュアル2007

    • Author(s)
      小池和彦
    • Total Pages
      135
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 肝癌疹療マニュアル2007

    • Author(s)
      小池 和彦
    • Total Pages
      135
    • Publisher
      医学書院
    • Related Report
      2007 Annual Research Report
  • [Book] 肝癌の診療-最新の進歩2006

    • Author(s)
      小池和彦
    • Total Pages
      340
    • Publisher
      日本メディカルセンター
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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