• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of molecular mechanism of leptin resistance, using transgenic mice over-expressing leptin

Research Project

Project/Area Number 12671079
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

INOUE Gen  Kyoto University, Department of Medicine, Lecturer, 医学研究科, 講師 (20260606)

Co-Investigator(Kenkyū-buntansha) OGAWA Yoshihiro  Kyoto University, Department of Medicine, Assistant professor, 医学研究科, 助手 (70291424)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsleptin resistance / high fat diet / hypothalamic feeding behavior regulating neuropeptides / transgenic mice / energy expenditure
Research Abstract

Clinical trial of recombinant leptin for the treatment of obesity is on going in the United States. However, it has been reported that the efficacy of leptin treatment by the peripheral administration is quite limited, probably because the most obese people may be in a leptin-resistant state. Recently, we developed transgenic mice over-expressing leptin, which have high sensitivity to leptin, despite an increased concentration of serum leptin comparable to that in obese people. In this project, we explored the pathogenic mechanism of leptin resistance by high fat meal using the transgenic mice and ob/ob mice, because we found that the transgenic mice also became obese by the load of high fat meal. However, we found that the induction of obesity by the high fat meal load was comparable in mice with different concentrations of serum leptin. Therefore, it is the most likely that leptin is neutral in the induction of obesity by high fat meal.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Aizawa-Abe M, et al.: "Pathophysiological role of leptin in obesity-related hypertension"J Clin. Invest.. 105(9). 1243-1252 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto Y, et al.: "Constitutively active mitogen-activated protein kinase kinase increases GLUT1 expression and recruits both GLUT1 and GLUT4 at the cell surface in 3T3-L1 adipocytes"Diabetes. 49(3). 332-339 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yura S, et al.: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin"J Clin. Invest.. 105(6). 749-755 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsuoka N, et al.: "Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin"Am J Physiol. Endocrinol Metab.. 280(2). E334-E339 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shintani M, et al.: "Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway"Diabetes. 50(2). 227-232 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonemitsu S, et al.: "Troglitazone induces GLUT4 translocation in L6 myotubes"Diabetes. 50(5). 1093-1101 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ebihara K, et al.: "Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes"Diabetes. 50(6). 1440-1448 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Son C, et al.: "Up-regulation of uncoupling protein 3 gene expression by fatty acids and agonists for ppars in 16 myotubes"Endocrinology. 142(10). 4189-4194 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue G, et al.: "Simultaneous onset of type I diabetes mellitus and painless thyroiditis following acute pancreatitis"Intern. Med.. 40(6). 515-518 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shintani M, et al.: "Troglitazone not only increases glut4 but also induces its translocation in rat adipocytes"Diabetes. 50(10). 2296-2300 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 井上 元: "脂肪細胞の分化とインスリン依存性糖輸送"分子糖尿病学の進歩-基礎から臨床まで-. 37-43 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 黄 真, 井上 元, 中尾一和: "肥満、高脂肪食によるインスリン依存性"内科. 87巻5号. 869-875 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 藤本宗也, 井上 元, 中尾一和: "Cushing症候群およびグルココルチコイド治療による糖尿病"糖尿病内分泌科-二次性糖尿病-. 13巻6号. 570-574 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 黄 真, 井上 元: "インスリン抵抗性症候群"糖尿病の治療と看護. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 則貞伸嘉, 井上 元, 中尾一和: "PPARのリガンドと活性化薬"炎症と免疫. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Aizawa-Abe, Y. Ogawa, H. Masuzaki, K. Ebihara, N. Satoh, H. Iwai, N, Matsuoka, T. Hayashi, K. Hosoda, G. Inoue, Y. Yoshimasa, K. Nakao.: "Pathophysiological role of leptin in obesity-related hypertension"J. Clin. Invest.. 105 : 9. 1243-1252 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Yamamoto, Y. Yoshimasa, M. Koh, J. Suga, H. Masuzaki, Y. Ogawa, K. Hosoda, H. Nishimura, Y. Watanabe, G. Inoue, K. Nakao: "Constitutively active MAP kinase kinase increases GLUT1 expression and recruits both GLUT1 and GLUT4 at the cell surface in 3T3-L1 adipocytes"Diabetes. 49 : 3. 332-339 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yura S, Ogawa Y, Sagawa N, Masuzaki H, Itoh H, Ebihara K, Aizawa-Abe M, Fujii S, Nakao K.: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin"J Clin Ihvest.. 105 : 6. 749-755 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsuoka N, Ogawa Y, Masuzaki H, Ebihara K, Aizawa-Abe M, Satoh N, Ishikawa E, Fujisawa Y, Kosaki A, Yamada K, Kuzuya H, Nakao K.: "Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin"Am J Physiol Endocrinol Metab.. 280 : 2. E334-339 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Shintani, Y. Ogawa, K. Ebihara, M. Aizawa-Abe, F. Miyanaga, K. Takaya, T. Hayashi, G. Inoue, K. Hosoda, M. Kojima, K. Kangawa, K. Nakao: "Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway"Diabetes. 50 : 2. 227-232 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S, Yonemitsu, H. Nishimura, M. Shintani, R. Inoue, Y. Yamamoto, H. Masuzaki, Y. Ogawa, K. Hosoda, G. Inoue, T. Hayashi, K. Nakao: "Troglitazone induces GLUT4 translocation in L6 myotubes"Diabetes. 50 : 5. 1093-1101 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Ebihara, Y. Ogawa, H. Masuzaki, M. Shintani, F. Miyanaga, M. Aizawa-Abe, T. Hayashi, K. Hosoda, G. Inoue, Y. Yoshimasa, O. Gavrilova, M.L. Reitman, K. Nakao: "Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes"Diabetes. 50 : 6. 1440-1448 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] C. Son, K. Hosoda, J. Matsuda, J. Fujikura, S. Yonemitsu, H. Iwakura, H. Masuzaki, Y. Ogawa, T. Hayashi, H. Itoh, H. Nishimura, G. Inoue, Y. Yoshimasa, Y. Yamori, K. Nakao: "Up-regulation of uncoupling protein 3 gene expression by fatty acids and agonists for ppars in 16 myotubes"Endocrinology. 142 : 10. 4189-4194 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue G, Sakurai T, Tanaka K, Akamizu T, Masuzaki H, Hosoda K, Hayashi T, Yoshimasa Y, Nakao K.: "Simultaneous onset of type 1 diabetes mellitus and painless thyroiditis following acute pancreatitis"Intern Med.. 40 : 6. 515-518 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Shintani, H. Nishimura, S. Yonemitsu, Y. Ogawa, T. Hayashi, K. Hosoda, G. Inoue, K. Nakao: "Troglitazone not only increases glut4 but also induces its translocation in rat adipocytes"Diabetes. 50 : 10. 2296-2300 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shintani M, et al.: "Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway"Diabetes. 50(2). 227-232 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yonemitsu S, et al.: "Troglitazone induces GLUT4 translocation in L6 myotubes"Diabetes. 50(5). 1093-1101 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ebihara K, et al.: "Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes"Diabetes. 50(6). 1440-1448 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Son C, et al.: "Up-regulation of uncoupling protein 3 gene expression by fatty acids and agonists for ppars in 16 myotubes"Endocrinology. 142(10). 4189-4194 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue G, et al.: "Simultaneous onset of type 1 diabetes mellitus and painless thyroiditis following acute pancreatitis"Intern. Med.. 40(6). 515-518 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shintani M, et al.: "Troglitazone not only increases glut4 but also induces its translocation in rat adipocytes"Diabetes. 50(10). 2296-2300 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 藤本宗也, 井上 元, 中尾一和: "Cushing症候群およびグルココルチコイド治療による糖尿病"糖尿病内分泌科-二次性糖尿病-. 13巻6号. 570-574 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 黄 真, 井上 元: "インスリン抵抗性症候群"糖尿病の治療と看護. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 則貞伸嘉, 井上 元, 中尾一和: "PPARのリガンドと活性化薬"炎症と免疫. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsuoka N, et al.: "Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin."Am J Physiol Endocrinol Metab.. 280(2). E334-E339 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Aizawa-Abe M,, et al.: "Pathophysiological role of leptin in obesity-related hypertension."J Clin Invest.. 105(9). 1243-1252 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamamoto Y, et al.: "Constitutively active mitogen-activated protein kinase kinase increases GLUT1 expression and recruits both GLUT1 and GLUT4 at the cell surface in 3T3-L1 adipocytes."Diabetes. 49(3). 332-339 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yura S, et al.: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin."J Clin Invest.. 105(6). 749-755 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 井上元: "脂肪細胞の分化とインスリン依存性糖輸送"分子糖尿病学の進歩-基礎から臨床まで-. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 黄真,井上元,中尾一和: "肥満、高脂肪食によるインスリン抵抗性"内科. 87巻5号. (2001)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi