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Prevention /reinstatement of obesity and fatty-liver resulted from estrogen-insufficiency by exercise

Research Project

Project/Area Number 13670145
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKOCHI MEDICAL SCHOOL

Principal Investigator

TODA Katsumi  KOCHI MEDICAL SCHOOL, MEDICINE ASSOCIATE PROFESSOR, 医学部, 助教授 (40197893)

Co-Investigator(Kenkyū-buntansha) SHIRAISHI Motonari  KOCHI MEDICAL SCHOOL, MEDICINE, TECHNICAL ASSISTANT, 動物実験施設, 教務職員 (80216184)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsEXERCISE / ESTROGEN / AROMATASE / KNOCK-OUT MOUSE / OBESITY / FATTY-LIVER / INSULIN / FENOFIBRATE / エストロゲン / 肥満 / フィブレート
Research Abstract

Introduction : Estrogen is a female steroid hormone, controlling various physiological functions. When the gene responsible for estrogen synthesis (Cyp19) was inactivated by targeting disruption in mice, various metabolic abnormalities including the obesity, fatty liver, and the insulin resistance of sugar metabolism were observed. This study is aiming to examine whether these phenotypes can be corrected not by the medicine but by exercise-load. Moreover, by combining exercise it was also examined whether the effect of the medicine prescribed for the mice could be reinforced. Result and Discussion : Exercise improve neither in glucose tolerance nor in insulin action in blood-glucose clearance test, significantly. Moreover, the mRNA levels of the acyl-CoA oxidase and catalase genes in the liver, and of the GLUT4 gene in muscles have not been improved by the exercise-load. However, mice treated both with exercise-load and with dietary fenofibrate, which is a hyperlipemia medicine, showed improvement in the insulin resistance phenotype of ArKO mice, when compared that of the mice loaded with exercise alone. These results demonstrate that although exercise alone does not improve the insulin resistance resulting from estrogen lack, it can reinforce the effects of the curative medicine. Clarification of molecular mechanisms underlying which exercise improves the abnormalities resulted from estrogen-insufficiency is a theme important to establish a cure with few side effects.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] K.Toda: "A loss of aggressive behaviour and its reinstatement by estrogen in mice lacking the aromatase gene (Cyp 19)"J. Endocrinol.. 168. 217-220 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Toda: "Oestrogen at neonatal stage is critical for reproductive ability of male mice as revealed by supplementation with 17β-oestradiol to aromatase (CPY19) gene"J. Endocrinol.. 168. 455-463 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Toda: "Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17β-oestradiol"J. Endocrinol.. 170. 99-111 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Toda: "Alternations in hepatic expression of fatty-acid metabolising enzymes in ArKO mice and their reversal by the treatment with 17β-estradiol or a peroxisome proliferator"J. Steroid. Biochem. Mol. Biol.. 79. 11-17 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] C.Miyaura: "Sex-and age-related response to aromatase-deficiency in bone"Biochem. Biophys. Res. Commun.. 280. 1062-1068 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Yoshikawa: "Aromatase-defiecient (ArKO) mice are retrieved from severe hepatic steatosis by peroxisome proliferator administration"Hepatology Research. 22. 278-287 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Toda: "Dietary bisphenol A prevents ovarian degeneration and bone Loss in female mice lacking the aromatase gene (Cyp19)"Eur. J. Biochemistry. 269. 2214-2222 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] C-L.Li: "Estrogen deficiency results in enhanced expression of Smoothened of the Hedgehog signaling in the thymus and affects thymocyte"Intermnational Immunopharmacol.. 2. 823-833 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Toda: "Fenofibrate, a ligand for PPARα, inhibits aromatase cytochrome P450 expression in the ovary of mouse"J. Lipid Res.. 44. 265-270 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Takeda: "Progressive development of insulin resistant phenotype in male mice lacking aromatase"J. Endocrinol. 176. 237-246 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Saibara: "Tamoxifen-induced nonalcholic steatohepatitis. in "HCV/Oxidative stress and liver disease (ed. K Okita)""Springer-Verlag. 96-104 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Toda: "A loss of aggressive behaviour and its reinstatement by estrogen in mice lacking the aromatase gene (Cyp 19)"J. Endocrinol.. 168. 217-220 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Toda: "Oestrogen at neonatal stage is critical for reproductive ability of male mice as revealed by supplementation with 17β-oestradiol to aromatase (CYP19) gene knockout mice"J. Endocrinol.. 168. 455-463 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Toda: "Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17β-oestradiol"J. Endocrinol.. 170. 99-111 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] C. Miyaura: "Sex- and age-related response to aromatase-deficiency in bone"Biochem. Biophys. Res. Commun.. 280. 1062-1068 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Yoshikawa: "Aromatase-defiecient (ArKO) mice 2002 are retrieved from severe hepatic steatosis by peroxisome proliferator administration"Hepatology Res.. 22. 278-287

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Toda: "Dietary bisphenol A prevents ovarian degeneration and bone Loss in female mice lacking the aromatase gene (Cyp19)"Eur. J. Biochemistry. 269. 2214-2222 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] C.-L. Li: "Estrogen deficiency results in enhanced expression of Smoothened of the Hedgehog signaling in the thymus and affects thymocyte development"International Immunopharmacol. 2. 823-833 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda K: "Progressive development of insulin resistant phenotype in male mice lacking aromatase gene (Cyp19)"J. Endocrinol. 176. 231-246 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Toda: "A loss of aggressive behaviour and its reinstatement by estrogen in mice lacking the aromatase gene (Cyp 19)"J.Endocrinol. 168. 217-220 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Toda: "Oestrogen at neonatal stage is critical for the reproductive ability of male mice as revealed by supplementation with 17β-oestradiol to aromatase (Cyp19) gene"J.Endocrinol. 168. 455-463 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Toda: "Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17β-oestradiol"J.Endocrinol. 170. 99-111 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Toda: "Alternations in hepatic expression of fatty-acid metabolising enzymes in ArKO mice and their reversal by the treatment with 17β-estradiol or a peroxisome proliferator"J. Steroid. Biochem. Mol. Biol.. 79. 11-17 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] C.Miyaura: "Sex-and age-related response to aromatase-deficiency in bone"Biochem. Biophys. Res. Commun.. 280. 1062-1068 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Yoshikawa: "Aromatase-defiecient (ArKO) mice are retrieved from severe hepatic steatosis by peroxisome proliferator administration"Hepatology Research. 22. 278-287 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Toda: "Dietary bisphenol A prevents ovarian degeneration and bone Loss in female mice lacking the aromatase gene (Cyp19)"Eur. J. Biochemistry. 269. 2214-2222 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] C.-L.Li: "Estrogen deficiency results in enhanced expression of Smoothened of the Hedgehog signaling in the thymus and affects thymocyte"Intermnational Immunopharmacol. 2. 823-833 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Toda: "Fenofibrate, a ligand for PPARα inhibits aromatase cytochrome P450 expression in the ovary of mouse"J. Lipid Res.. 44. 265-270 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Takeda: "Progressive development of insulin resistant phenotype in male mice lacking aromatase"J. Endocrinol. 176. 237-246 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Saibara: "Tamoxifen-induced nonalcholic steatohepatitis. in "HCV/Oxiclative stress and liver disease (ed. K Okita)""Springer-Verlag. 96-104 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Yoshikawa: "Aromatase-defiecient (ArKO) mice are retrieved from severe hepatic steatosis by peroxisome proliferator administration"Hepatology Research. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Toda: "Alterations in hepatic expression of fatty-acid metabolising enzymes in ArKO mice and their reversal by the treatment with 17 β-estradiol or a peroxisome proliferator"J.Steroid.Biochem.Mol.Biol.. 79. 11-17 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 戸田 勝己: "エストロゲン欠乏によっておきる肥満症の分子遺伝学的解析とその治療法の確立"臨床成人病. 31. 1382-1383 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 西原 利治: "エストロゲン合成酵素遺伝子の欠損に起因する脂肪酸の代謝異常と生殖機能異常の解析"ホルモンと臨床. 49. 161-166 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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