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Research of the regulation of adipase mass through angiogenesis induced by the endothelin system

Research Project

Project/Area Number 18590813
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKobe University

Principal Investigator

EMOTO Noriaki  Kobe University, Graduate School of Medicine, Assistant Professor (30294218)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsEndothelin / Obesity / Angiopenesis
Research Abstract

Our Specific Aims of the research proposal and Results obtained were as follows:
1. To elucidate the molecular mechanisms of ET-1 produced from endothelial cell in impaired angiogenesis in adipose tissue growth.
Examination of oxygen consumption and respiratory quotient at 8 weeks of age showed no significant differences between WT and KO mice. There were no significant differences in locomotor activity and body temperature assessed by implanted radio frequency telemetry. Food consumption adjusted for mouse weight was not different between WT and KO mice. Vascular density in endothelin-1 deficient mice was decreased as compared to WT mice, indicating that retarded adipose mass growth in KO mice correlated with decreased vascular formation.
2. To examine whether anti-obesity phenotype in ET-1 KO mice leads to the prevention for obesity-related disorders.
We found that mice lacking endothelin-1 in vascular endothelial cells resist the development of diet-induced obesity, hypertension, and insulin resistance.
3. To investigate the possibility whether the endothelin system could be a therapeutic target for obesity and the related disorders.
ET-1 KO mice were mated with mice models of genetic obesity and insulin resistance to produce double mutant mice. We used two different kinds of obesity models, ob/ob and KKAy mice. We demonstrated that endothelin-1 has an important role for inducing inflammation in adipose tissue.

Report

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

    (23 results)

All 2007 2006

All Journal Article (14 results) (of which Peer Reviewed: 5 results) Presentation (9 results)

  • [Journal Article] Obesity-induced upregulation of myocardial endothelin-1 expression is mediated by leptin2007

    • Author(s)
      Adiarto S
    • Journal Title

      Biochem Biophys Res Commun 353

      Pages: 623-627

    • 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] Circadian expression of clock genes in human peripheral leukocytes2007

    • Author(s)
      Fukuya H
    • Journal Title

      Biochem Biophys Res Commun 354

      Pages: 924-928

    • 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] Local overexpression of toll-like receptors at the vessel wall induces atherosclerotic lesion formation: synergism of TLR2 and TLR4.2007

    • Author(s)
      Shinohara, M
    • Journal Title

      Arterioscler Thromb Vasc Biol. 27

      Pages: 2384-2391

    • 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] Obesity-induced upregulation of myocardial endothelin-1 expression is mediated by leptin2007

    • Author(s)
      Adiarto, S, Emoto, N, Iwasa, N, Yokoyama, M
    • Journal Title

      Biochem Biophys Res Commun 353

      Pages: 623-627

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Circadian expression of clock genes in human peripheral leukocytes2007

    • Author(s)
      Fukuya, H, Emoto, N, Nonaka, H, Yagita, K, Okamura, H, Yokoyama, M
    • Journal Title

      Biochem Biophys Res Commun 354

      Pages: 924-928

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Local overexpression of toll-like receptors at the vessel wall induces atherosclerotic lesion formation: synergism of TLR2 and TLR42007

    • Author(s)
      Shinohara, M, Hirata, K, Yamashita, T, Takaya, T, Sasaki, N, Shiraki, R, Ueyama, T, Emoto, N, Inoue, N, Yokoyama, M, Kawashima, S
    • Journal Title

      Arterioscler Thromb Vase Biol 27

      Pages: 2384-2391

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Local overexpression of toll-like receptors at the vessel wall induces atherosclerotic lesion formation: synergism of TLR2 and TLR4.2007

    • Author(s)
      Shinohara M.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 27

      Pages: 2384-2391

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] エンドセリン受容体拮抗薬・エンドセリン変換酵素阻害薬2007

    • Author(s)
      江本憲昭
    • Journal Title

      循環器科 62

      Pages: 439-445

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Obesity-induced upregulation of myocardial endothelin-1 expression is mediated by leptin.2007

    • Author(s)
      Adiarto Suko
    • Journal Title

      Biochem Biophys Res Commun. 353

      Pages: 623-627

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Circadian expression of clock genes in human peripheral leukocytes.2007

    • Author(s)
      Fukuya Hiroyuki
    • Journal Title

      Biochem Biophys Res Commun. 354

      Pages: 924-928

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibitory effect of insulin on vasopressin-induced intracellular calcium response is blunted in hyperinsulinemic hypertensive patients: role of membrane fatty acid composition2006

    • Author(s)
      Maekawa K
    • Journal Title

      Heart Vessels 21

      Pages: 205-212

    • 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] Inhibitory effect of insulin on vasopressin-induced intracellular calcium response is blunted in hyperinsulinemic hypertensive patients: role of membrane fatty acid composition2006

    • Author(s)
      Maekawa, K, Tsujino, T, Saito, K, Kim, JI, Ikeda, Y, Emoto, N, Yokoyama, M
    • Journal Title

      Heart Vessels 21

      Pages: 205-212

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Genetically modified rodent models in the endothelin-related genes.2006

    • Author(s)
      Emoto Norikai
    • Journal Title

      Nippon Rinsyo 64

      Pages: 311-315

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibitory effect of insulin on vasopressin-induced intracellular calcium response is blunted in hyperinsulinemic hypertensive patients : role of membrane fatty acid composition.2006

    • Author(s)
      Maekawa Kouichi
    • Journal Title

      Heart Vessels 21

      Pages: 205-212

    • Related Report
      2006 Annual Research Report
  • [Presentation] 遺伝子操作動物を用いたエンドセリンシステムの心血管病における役割2007

    • Author(s)
      江本憲昭
    • Organizer
      第48回日本脈管学会総会
    • Place of Presentation
      松本
    • Year and Date
      2007-10-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] Attenuation of angiogenesis and macrophage accumulation in adipose tissue in vascular endothelial endothelin-1 knockout mice2007

    • Author(s)
      Iwasa, N
    • Organizer
      ET-10: Tenth International Conference on Endothelin
    • Place of Presentation
      Bergamo, Italy
    • Year and Date
      2007-09-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The effects of a dual endothelin receptor antagonist, bosentan, on metabolic parameters in the patients with pulmonary hypertension2007

    • Author(s)
      Iwasa, N
    • Organizer
      ET-10: Tenth International Conference on Endothelin
    • Place of Presentation
      Bergamo, Italy
    • Year and Date
      2007-09-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The effects of a dual endothelia receptor antagonist, bosentan, on metabolic parameters in the patients with pulmonary hypertension2007

    • Author(s)
      Iwasa, N., Nakayama, K., Miyagawa, K., Nonaka, H., Emoto, N
    • Organizer
      ET-10: Tenth International Conference on Endothelin
    • Place of Presentation
      Bergamo, Italy
    • Year and Date
      2007-09-16
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Dissection of roles of ET-1 in cardiovascular system: lesion from genetically modified mice2007

    • Author(s)
      Emoto, N
    • Organizer
      The 71st Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Kobe
    • Year and Date
      2007-03-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Endothelial Cell-restricted Inactivation of Endothelin-1 revealed its Unexpected Rolc in the Regulation of Adipose Tissue Mass Accumulation through its Angiogenic Property2006

    • Author(s)
      Adiarto, S
    • Organizer
      79th the Scientific Sessions of the American Heart Association
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2006-11-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Attenuation of Diet-Induced Obesity, Hypertension and Insulin Resistance in Vascular Endothelial Endothelin-1 Knockout Mice2006

    • Author(s)
      Iwasa, N
    • Organizer
      79th the Scientific Sessions of the American Heart Association
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2006-11-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Endothelial Cell-restricted Inactivation of Endothelin-1 revealed its Unexpected Role in the Regulation of Adipose Tissue Mass Accumulation through its Angiogenic Property2006

    • Author(s)
      Adiarto, S., Emoto, N., Iwasa, N., Raharjo, SB., Nakayama, K., Anggrahini, WD., Widyantro, B., Nonaka, H., Masuda, Y., Suzuki, T., Kisanuki, YY, Yanagisawa, M., Yokoyama, M
    • Organizer
      79th the Scientific Sessions of the American Heart Association
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2006-11-12
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Unexpected Role of Vascular Endothelial Endothelin-1 in the Regulation of Blood Pressure and Adipose Tissue Mass Accumulation revealed by Conditional Knock-out Study2006

    • Author(s)
      Adinrto, S
    • Organizer
      The 21st Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Hakata
    • Year and Date
      2006-10-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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

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