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Elucidation of novel mechanisms of obesity and the therapeutic drug -elucidation of leptin resistance-

Research Project

Project/Area Number 21790079
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionHiroshima University

Principal Investigator

HOSOI Toru  Hiroshima University, 大学院・医歯薬学総合研究科, 講師 (40379889)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords小胞体ストレス / 肥満 / レプチン / レプチン抵抗性
Research Abstract

Leptin is mainly secreted from adipose tissue, which subsequently induces anti-obesity action. On the other hand, it has been reported that most of the obesity patients are in the state of "leptin resistance" , which cannot adequately respond to the circulating leptin. At these circumstances, we found the possibility that "endoplasmic reticulum (ER) stress" is involved in the development of leptin resistance. Accumulation of unfolded protein will result in ER stress and increasing evidence has been suggested that ER stress is involved in several types of diseases. In the present study, we found the novel drug, which can reduce ER stress. Moreover, subsequent analysis indicated that this drug could inhibit high-fat diet-induced obesity in mice model.

Report

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

    (30 results)

All 2011 2010 2009 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (15 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Homocysteine induces X-box binding protein 1 splicing in the mice brain.2010

    • Author(s)
      Hosoi T., Ogawa K., Ozawa K.
    • Journal Title

      Neurochemistry International 56

      Pages: 216-220

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] MyD88 plays a key role in LPS-induced Stat3 activation in the hypothalamus.2010

    • Author(s)
      Yamawaki Y., Kimura H., Hosoi T., Ozawa K.
    • Journal Title

      American Journal of Physiology Regulatory Integrative and Comparative Physiology 298

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A unique modulator of endoplasmic reticulum stress-signalling pathways : the novel pharmacological properties of amiloride in glial cells.2010

    • Author(s)
      Hosoi T., Kume A., Otani K., Oba T., Ozawa K.
    • Journal Title

      British Journal of Pharmacology 159

      Pages: 428-437

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Myeloid Differentiation Factor 88 (MyD88)-Deficiency Increases Risk of Diabetes in Mice.2010

    • Author(s)
      Hosoi T, Yokoyama S, Matsuo S, Akira S, Ozawa K
    • Journal Title

      PLoS ONE 5(9)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] TEK/Tie2 is a novel gene involved in endoplasmic reticulum stress.2010

    • Author(s)
      Hosoi T., Tamubo T., Horie N., Okuma Y., Nomura Y., Ozawa K.
    • Journal Title

      Journal of Pharmacological Science 114

      Pages: 230-233

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endoplasmic reticulum stress in disease : mechanisms and therapeutic opportunities.2010

    • Author(s)
      Hosoi T., Ozawa K.
    • Journal Title

      (2010)Clinical Science (Lond). 118

      Pages: 19-29

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice.2010

    • Author(s)
      Hosoi T
    • Journal Title

      PLoS One

      Volume: 5 Pages: 1-7

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TEK/Tie2 is a novel gene involved in endoplasmic reticulum stress.2010

    • Author(s)
      Hosoi T
    • Journal Title

      J Pharmacol Sci

      Volume: 114 Pages: 230-233

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homocysteine induces X-box-binding protein 1 splicing in the mice brain.2010

    • Author(s)
      Hosoi T
    • Journal Title

      Neurochem Int. 56

      Pages: 216-220

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A unique modulator of endoplasmic reticulum stress-signalling pathways : the novel pharmacological properties of amiloride in glial cells.2010

    • Author(s)
      Hosoi T
    • Journal Title

      Br J Pharmacol. 159

      Pages: 428-437

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endoplasmic reticulum stress in disease : mechanisms and therapeutic opportunities.2010

    • Author(s)
      Hosoi T
    • Journal Title

      Clin Sci (Loud). 118

      Pages: 19-29

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MyD88 plays a key role in LPS-induced Stat3 activation in the hypothalamus.2010

    • Author(s)
      Yamawaki Y
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol. 298

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of endoplasmic reticulum stress in obesity associated with leptin resistance.2009

    • Author(s)
      Hosoi T, Ozawa K.
    • Journal Title

      Journal of Medical Investigation 56

      Pages: 296-8

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] 小澤孝一郎小胞体ストレスと免疫応答活性化による新規アルツハイマー病発症機構2011

    • Author(s)
      細井徹
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Related Report
      2010 Final Research Report
  • [Presentation] 生活習慣病の新機構解明と次世代型治療薬の開発研究2011

    • Author(s)
      細井徹
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Related Report
      2010 Final Research Report
  • [Presentation] 生活習慣病の新機構解明と次世代型治療薬の開発研究2011

    • Author(s)
      細井徹
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡(奨励賞講演 招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 小胞体ストレスと免疫応答活性化による新規アルツハイマー病発症機構2011

    • Author(s)
      細井徹
    • Organizer
      日本薬学会第131年会(シンポジウム)
    • Place of Presentation
      静岡(招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 小澤孝一郎アルツハイマー病発症に関わる小胞体ストレスと免疫応答の新規メカニズム2010

    • Author(s)
      細井徹、大庭達哉、本多美耶、大熊康修、野村靖幸
    • Organizer
      第37回日本脳科学会
    • Place of Presentation
      天津医科大学国際会議センター(中国)
    • Related Report
      2010 Final Research Report
  • [Presentation] MyD88遺伝子欠損による糖尿病誘発2010

    • Author(s)
      細井徹、横山匠太、松尾俊、小澤孝一郎
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Related Report
      2010 Final Research Report
  • [Presentation] Endoplasmic reticulum stress induces leptin resistance.2010

    • Author(s)
      Hosoi T.
    • Organizer
      Experimental Biology2010
    • Place of Presentation
      Anaheim, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Endoplasmic reticulum stress induces leptin resistance.2010

    • Author(s)
      Hosoi T.
    • Organizer
      Experimental Biology2010
    • Place of Presentation
      Anaheim, USA(招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] アルツハイマー病発症に関わる小胞体ストレスと免疫応答の新規メカニズム2010

    • Author(s)
      細井徹
    • Organizer
      第37回日本脳科学会
    • Place of Presentation
      天津医科大学 国際会議センター(中国)
    • Related Report
      2010 Annual Research Report
  • [Presentation] グリア細胞におけるIL-6産生調節系への小胞体ストレスの関与の可能性2009

    • Author(s)
      細井徹、大庭達哉、本多美耶、小澤孝一郎
    • Organizer
      第14回グリア研究会
    • Place of Presentation
      大阪市
    • Year and Date
      2009-11-14
    • Related Report
      2010 Final Research Report
  • [Presentation] Leptin resistance associated with obesity would be mediated through endoplasmic reticulum stress.2009

    • Author(s)
      Hosoi T., Sasaki M., Miyahara T., Hashimoto C., Matsuo S., Yoshii M., Ozawa K.
    • Organizer
      4th Cell Stress Society International (CSSI) Congress on Stress Responses in Biology and Medicine
    • Place of Presentation
      Sapporo, Japan.
    • Related Report
      2010 Final Research Report
  • [Presentation] Possible involvement of endoplasmic reticulum stress in obesity associated with leptin resistance.2009

    • Author(s)
      Hosoi T., Sasaki M., Miyahara T., Hashimoto C., Matsuo S., Yoshii M., Ozawa K.
    • Organizer
      The 11th International Symposium on Exocrine Secretion, Tokushima 09
    • Place of Presentation
      Tokushima, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] 肥満の中枢機構:小胞体ストレスによる視床下部レプチン受容体応答活性低下の関与2009

    • Author(s)
      細井徹、大熊康修、野村靖幸、小澤孝一郎
    • Organizer
      第36回日本脳科学会
    • Place of Presentation
      金沢市
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Possible involvement of endoplasmic reticulum stress in obesity associated with leptin resistance2009

    • Author(s)
      Hosoi T
    • Organizer
      The 11th International Symposium on Exocrine Secretion, Tokushima 09
    • Place of Presentation
      Tokushima, Japan
    • Related Report
      2009 Annual Research Report
  • [Presentation] Leptin resistance associated with obesity would be mediated througt endoplasmic reticulum stress.2009

    • Author(s)
      Hosoi T
    • Organizer
      4th Cell Stress Society International (CSSI) Congress on Stress Responses in Biology and Medicine
    • Place of Presentation
      Sapporo, Japan.
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://home.hiroshima-u.ac.jp/tiryou/index.htm

    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] レプチン抵抗性を改善および/または予防するための薬学的組成物、並びにその使用2010

    • Inventor(s)
      細井徹, 小澤孝一郎
    • Industrial Property Rights Holder
      国立大学法人広島大学
    • Filing Date
      2010-04-14
    • Related Report
      2010 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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