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Molecular mechanism of cardiac hypertrophy caused by lipid toxicity

Research Project

Project/Area Number 16590250
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKagoshima University

Principal Investigator

HORIUCHI Masahisa  Kagoshima University, Graduate School of Medical and Dental Sciences, Assistant Professor, 大学院・医歯学総合研究科, 講師 (50264403)

Co-Investigator(Kenkyū-buntansha) SAHEKI Takeyori  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (10056070)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordscarnitine / cardiac hypertrophy / fatty aicd / JVS mice / pyruvate dehydrogenase kinae / orexin / 脂肪酸毒性 / PPARα
Research Abstract

[Purpose] To elucidate the mechanism of the cardiac hypertrophy of JVS mice.
1)We examined the development of cardiac hypertrophy in juvenile visceral steatosis (JVS) mice, a model of systemic carnitine deficiency, by varying the amount of lipid in the diet. Cardiac hypertrophy was markedly attenuated by decreasing soy bean oil (SBO) from 5% (w/w) to 1%. Triglyceride contents of ventricle in JVS mice fed 1% SBO were significantly lower than that in JVS mice fed 5% SBO. Addition of medium-chain triglyceride metabolically utilized by JVS mice did not affect the development of cardiac hypertrophy. On the other hand, the mRNA levels of atrial natriuretic peptide and skeletal α-actin, which are related to cardiac hypertrophy, were also attenuated by decreasing lipid in the diet. Adenylate energy charge and creatine phosphate in the heart of JVS mice at the early stage of hypertrophy were not significantly different from control mice given the same laboratory chow (4.6% of lipid). Although ur … More inary prostaglandin F_<2α> was found to be increased in JVS mice at 15 days of age when they developed cardiac hypertrophy, administration of aspirin was not efficacious. We therefore propose that the proportion of lipid in the diet is important in the development of cardiac hypertrophy in carnitine-deficient JVS mice, and that this is not related to prostaglandin formation.
2)We found reduced locomotor activity (LA) under fasting in JVS mice. LA recovered under carnitine or sucrose administration, but not under medium-chain triglyceride. In addition, fasted JVS mice, without any energy supply, were activated by modafinil, a stimulator of the dopamine pathway. These results suggest that the reduced LA is not adequately explained by energy deficit. We found lower percentage of c-Fos positive orexin neurons in the lateral hypothalamus and reduced orexin-A concentration in the cerebrospinal fluid of fasted JVS mice. These results strongly suggest that the reduced LA in fasted jvs^<-/-> mice is related to the inhibition of orexin neuronal activity. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (15 results)

All 2006 2004

All Journal Article (13 results) Book (2 results)

  • [Journal Article] Attenuation of cardiac hypertrophy in carnitine-deficient juvenile visceral steatosis(JVS) mice achieved by lowering dietary lipid.2006

    • Author(s)
      Md Abdul Jalil, Masahisa Horiuchi, et al.
    • Journal Title

      J Biochem 139・2

      Pages: 263-270

    • NAID

      10018847819

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice.2006

    • Author(s)
      Goichiro Yoshida, Meng Xian Li, Masahisa Horiuchi, et al.
    • Journal Title

      Neurosci Res 55・1

      Pages: 78-86

    • NAID

      10020616692

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Attenuation of cardiac hypertrophy in carnitine-deficient juvenile visceral steatosis (JVS) mice achieved by lowering dietary lipid.2006

    • Author(s)
      Md.Abdul Jalil, Masahisa Horiuchi, et al.
    • Journal Title

      J Biochem. 139

      Pages: 263-270

    • NAID

      10018847819

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fasting-induced reduction in locomotor activity and reduced response of prexin neurons in carnitine-deficient mice.2006

    • Author(s)
      Goichiro Yoshida, Meng Xian Li, Masahisa Horiuchi, et al.
    • Journal Title

      Neurosci Res 55

      Pages: 78-86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Attenuation of Cardiac Hypertrophy in Carnitine-Deficient Juvenile Visceral Steatosis (JVS) Mice Achieved by Lowering Dietary Lipid2006

    • Author(s)
      Md.Abdul Jalil, et al.
    • Journal Title

      J Biochem 139・2

      Pages: 263-270

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice2006

    • Author(s)
      Goichiro Yoshida, et al.
    • Journal Title

      Neuroscience Research (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] カルニチン欠乏・脂質代謝と疲労2004

    • Author(s)
      堀内正久, 他
    • Journal Title

      Molecular Medicine 41・10

      Pages: 1235-1242

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Purification and expression of a processing protease on β-alanine-oxoglutarate aminotransferase from rat liver mitochondria2004

    • Author(s)
      Tomoko Ohyama, et al.
    • Journal Title

      FEBS Lett 572・1-3

      Pages: 251-255

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] カルニチンの生体作用2004

    • Author(s)
      佐伯 武頼
    • Journal Title

      ビタミン 78・11

      Pages: 545-554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Purification and expression of a processing protease on β-alanine-oxoglutarate aminotransferase from rat liver mitochindria2004

    • Author(s)
      Tomoko Ohyama, et al.
    • Journal Title

      FEBS Lett. 572

      Pages: 251-255

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] カルニチン欠乏・脂質代謝と疲労2004

    • Author(s)
      堀内正久, 他
    • Journal Title

      Molecular Medicine 41

      Pages: 1235-1242

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Purification and expression of a processing protease on β-alanine-oxoglutarate aminotransferase from rat liver mitochondria.2004

    • Author(s)
      Tomoko Ohyama, et al.
    • Journal Title

      FEBS Lett 572

      Pages: 251-255

    • Related Report
      2004 Annual Research Report
  • [Journal Article] カルニチンの生体作用 -カルニチン欠損マウスを用いた解析から-Bio-Function of Carnitine -Consideration from Analysis of Carnitine-Deficient Mice-2004

    • Author(s)
      佐伯武頼
    • Journal Title

      ビタミン 78

      Pages: 545-554

    • Related Report
      2004 Annual Research Report
  • [Book] モデル動物の作製と維持(編集 : 森脇和郎、山村研一、米川博通)2004

    • Author(s)
      佐伯武頼, 小林圭子, 堀内正久(分担)
    • Total Pages
      956
    • Publisher
      エル・アイ・シー(Life-Science Information Center)東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] モデル動物の作製と維持(編集:森脇和郎, 山村研一, 米川博通)2004

    • Author(s)
      佐伯武頼, 小林圭子, 堀内正久(分担)
    • Total Pages
      956
    • Publisher
      エル・アイ・シー(Life-Science Information Center)(東京)
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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