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Analysis of the paradoxical correlation between hepatic insulin resistance and oxidative stress in the pathogenesis of steatohepatitis

Research Project

Project/Area Number 20590796
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKeio University

Principal Investigator

TOMITA Kengo  Keio University, 医学部, 共同研究員 (50317129)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Takahiko  (財)東京都高齢者研究・福祉振興財団, 東京都老人総合研究所, 研究員 (40301791)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords酸化ストレス / インスリン抵抗性 / 脂肪肝炎 / 急性肝障害 / 肝細胞癌 / 肝再生 / 内科 / 糖尿病 / シグナル伝達
Research Abstract

Given the growing number of metabolic syndrome patients in recent years, the incidence of nonalcoholic steatohepatitis increases in Japan. Adiponectin, an adipocytokine, is released by adipose tissue and improves insulin resistance. AdipoR2, one of the adiponectin receptors, is expressed predominantly in the liver. In the present study, we have found that hepatic adiponectin sensitivity and resistance mediated by adiponectin/AdipoR2 signaling plays a significant role in the pathogenesis of nonalcoholic steatohepatitis. Thus, the liver AdipoR2 signaling pathway could be a promising target in treating nonalcoholic steatohepatitis.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (16 results)

All 2011 2010 2009 2008 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] Plasma free myristic acid proportion is a predictor of nonalcoholic steatohepatitis.2011

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

      Dig Dis Sci (in press.)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fbxw7 controls lipid metabolism and cell fate decision in the liver.2011

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

      J Clin Invest 121

      Pages: 342-354

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Insulin receptor mutation results in insulin resistance and hyperinsulinemia but does not exacerbate Alzheimer's-like phenotypes in mice.2011

    • Author(s)
      Shimizu T, et al.
    • Journal Title

      Biochem Biophys Res Commun (in press.)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver.2011

    • Author(s)
      Onoyama I, Suzuki A, Matsumoto A, Tomita K, et al.
    • Journal Title

      The Journal of Clinical Investigation

      Volume: 121 Pages: 342-354

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxidative stress in skeletal muscle causes severe disturbance of exercise activity without muscle atrophy.2010

    • Author(s)
      Shimizu T, et al.
    • Journal Title

      Free Radic Biol Med 48

      Pages: 1252-1262

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Utility of quantitative 99mTc-phytate scintigraphy to diagnose early-stage non-alcoholic steatohepatitis.2009

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

      Scand J Gastroenterol 44

      Pages: 229-236

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase-derived PGD2 biosynthesis.2009

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

      J Clin Invest 119

      Pages: 1477-1488

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conditional knockout of Mn-SOD targeted to type IIB skeletal muscle fibers increases oxidative stress and is sufficient to alter aerobic exercise capacity.2009

    • Author(s)
      Shimizu T, et al.
    • Journal Title

      Am J Physiol Cell Physiol 297

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Skin atrophy in cytoplasmic SOD-deficient mice and its complete recovery using a vitamin C derivative.2009

    • Author(s)
      Shimizu T, et al.
    • Journal Title

      Biochem Biophys Res Commun 382

      Pages: 457-461

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic AdipoR2 signaling plays a protective role aganist progression of nonalcoholic steatohepatitis in mice.2008

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

      Hepatology 48

      Pages: 458-473

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluating the severity of nonalcoholic steatohepatitis with superparamagnetic iron oxide-enhanced magnetic resonance imaging.2008

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

      J Magn Reson Imaging 28

      Pages: 1444-1450

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice.2008

    • Author(s)
      Shimizu T, et al.
    • Journal Title

      Am J Pathol 129

      Pages: 291-298

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic AdipoR2 signaling plays a protective role against progression of nonalcoholic steatohepatitis.2008

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

      Hepatology 48

      Pages: 458-473

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 非アルコール性脂肪肝炎(nonalcoholic steatohepatitis : NASH)発症・進展における、adiponectin/AdipoR2シグナルの果たす役割に関する検討2009

    • Author(s)
      冨田謙吾
    • Organizer
      第5回宮崎サイエンスキャンプ
    • Place of Presentation
      宮崎
    • Year and Date
      2009-02-20
    • Related Report
      2010 Final Research Report
  • [Presentation] 非アルコール性脂肪肝炎病態機序における、抗酸化酵素catalaseを介した肝臓アディポネクチン感受性・抵抗性の役割に関する検討2008

    • Author(s)
      冨田謙吾
    • Organizer
      日本応用酵素協会第34回研究発表会
    • Place of Presentation
      大阪
    • Year and Date
      2008-11-17
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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