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Development of novel drug for obesity targeting endoplasmic reticulum stress

Research Project

Project/Area Number 22590100
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionHiroshima University

Principal Investigator

OZAWA Koichiro  広島大学, 医歯薬保健学研究院, 教授 (10211822)

Co-Investigator(Kenkyū-buntansha) TAKEDA Kei  広島大学, 大学院・医歯薬保健学研究院, 教授 (30135032)
HOSOI Toru  広島大学, 大学院・医歯薬保健学研究院, 講師 (40379889)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsレプチン抵抗性 / 小胞体ストレス / レプチン / 抗肥満薬 / 肥満
Research Abstract

Obesity is one of major risk factor of metabolic syndrome. Previous study indicated that endoplasmic reticulum (ER) stress may be involved in development of “leptin resistance”, an insensitivity of anti-obesity hormone leptin. In the present study, we aimed to develop novel brain-transitional drug for attenuating ER stress and “leptin resistance”, based on the structure of drug which we identifiedpreviously. We analyzed pharmacological property of this drug. Moreover, we investigated whether this drug has anti-obesity action using mice model of high-fat diet-induced obesity.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (36 results)

All 2013 2012 2011 2010 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (16 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Inhibition of casein kinase 2 modulates XBP1-GRP78 arm of unfolded protein responses in cultured glial cells2012

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

      PLoS One

      Volume: 7(6)

    • NAID

      120005300501

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fluvoxamine attenuated endoplasmic reticulum stress-induced leptin resistance2012

    • Author(s)
      Hosoi T, Miyahara T, Kayano T, Yokoyama S, Ozawa K
    • Journal Title

      Front Endocrinol (Lausanne)

      Volume: 3(12) Pages: 1-5

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's disease: endoplasmic reticulum stress and immunological stress in pathogenesis of Alzheimer's disease2012

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

      J Pharmacol Sci

      Volume: 118(3) Pages: 319-24

    • NAID

      10030455370

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stearoyl-CoA Desaturase 1 (SCD1) is a key factor mediating diabetes in MyD88-deficient mice2012

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

      Gene

      Volume: 497(2) Pages: 340-3

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective effects of 4-phenylbutyrate derivatives on the neuronal cell death and endoplasmic reticulum stress2012

    • Author(s)
      Mimori S, Okuma Y, Kaneko M, Kawada K, Hosoi T, Ozawa K, Nomura Y, Hamana H
    • Journal Title

      Biol Pharm Bull

      Volume: 35(1) Pages: 84-90

    • NAID

      130001872347

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biological mechanism in antidepressant-like effect of sodium butyrate (HDAC inhibitor).2012

    • Author(s)
      Yousuke Yamawaki
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 118(S1)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exploration of a new class of anti-obesity agents which targets ER sress.2012

    • Author(s)
      Rie Yamaguchi
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 118(S1)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel compound ameliorating leptin resistance induced by endoplasmic reticulum stress in obesity.2012

    • Author(s)
      Keisuke Toyoda
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 118(S1)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of casein kinase 2 modulates XBP1-GRP78 arm of unfolded protein responses in cultured glial cells.2012

    • Author(s)
      Toru Hosoi
    • Journal Title

      PLoS ONE

      Volume: 7

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enantioselective trapping of an a-chiral carbanion of acyclic nitrile by a carbon electrophile.2012

    • Author(s)
      Michiko Sasaki
    • Journal Title

      Chemical Communications

      Volume: 48 Pages: 2897-2899

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluvoxamine attenuated endoplasmic reticulum stress-induced leptin resistance2012

    • Author(s)
      Hosoi T
    • Journal Title

      Frontiers in Endocrinology

      Volume: 3 Pages: 1-5

    • DOI

      10.3389/fendo.2012.00012

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective Effects of 4-Phenylbutyrate Derivatives on the Neuronal Cell Death and Endoplasmic Reticulum Stress2012

    • Author(s)
      Mimori S、Okuma Y、Kaneko M、Kawada K、Hosoi T、Ozawa K、Nomura Y、Hamana H
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 35 Issue: 1 Pages: 84-90

    • DOI

      10.1248/bpb.35.84

    • NAID

      130001872347

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stearoyl-CoA Desaturase 1 (SCD1) is a key factor mediating diabetes in MyD88-deficient mice2012

    • Author(s)
      Yokoyama S
    • Journal Title

      Gene

      Volume: (in press) Issue: 2 Pages: 340-343

    • DOI

      10.1016/j.gene.2012.01.024

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer&rsquo;s Disease:<BR>Endoplasmic Reticulum Stress and Immunological Stress in Pathogenesis of Alzheimer&rsquo;s Disease2012

    • Author(s)
      Hosoi T
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 118 Issue: 3 Pages: 319-324

    • DOI

      10.1254/jphs.11R09FM

    • NAID

      10030455370

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TEK/Tie2 is a novel gene involved in endoplasmic reticulum stress2010

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

      J Pharmacol Sci

      Volume: 114(2) Pages: 230-3

    • NAID

      10027746811

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice2010

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

      PLoS One

      Volume: 5(9)

    • NAID

      120002737828

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Myeloid differentiation factor 88 (MyD88)-deficiencyincreases 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
  • [Presentation] 小胞体ストレスを標的とした新規抗肥満薬の探索2013

    • Author(s)
      山口 理恵、細井 徹、馬場 幸子、豊田 圭亮、野地 紀久子、小澤 光一郎
    • Organizer
      第85回 日本薬理学会年会
    • Place of Presentation
      京都市
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規核膜Ca2+チャネル、核膜Orail1様タンパク質の発現について2013

    • Author(s)
      吉井美智子
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肥満における小胞体ストレス誘導性のレプチン抵抗性改善化合物の探索2012

    • Author(s)
      豊田圭亮、細井 徹、小澤光一郎
    • Organizer
      第85回 日本薬理学会年会
    • Place of Presentation
      京都市
    • Related Report
      2012 Final Research Report
  • [Presentation] 3T3-L1 脂肪細胞分化に対するカルシウムイオンチャネル阻害剤の影響2012

    • Author(s)
      高橋知子
    • Organizer
      第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Place of Presentation
      松江市
    • Related Report
      2012 Annual Research Report
  • [Presentation] レプチンシグナルに対するアデノシンの作用機構の解析2012

    • Author(s)
      清水薫
    • Organizer
      第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Place of Presentation
      松江市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 小胞体ストレスによるレプチン抵抗性を標的とした生活習慣病に対する創薬ターゲットの探索2011

    • Author(s)
      細井 徹、馬場 幸子、松尾 俊、山口 理恵、豊田 圭亮、茅野貴秋、小澤 光一郎
    • Organizer
      第6回小胞体ストレス研究会
    • Place of Presentation
      岡山市
    • Year and Date
      2011-10-28
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] MyD88遺伝子欠損による糖尿病発症機構の解明~コレステロール合成制御異常の関与~2011

    • Author(s)
      横山匠太、細井 徹、小澤光一郎
    • Organizer
      第120回日本薬理学会近畿部会
    • Place of Presentation
      京都市
    • Year and Date
      2011-01-11
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] 肥満脳におけるレプチン受容体応答系抑制機構の解明と創薬:小胞体ストレスの関与2011

    • Author(s)
      細井 徹、馬場 幸子、松尾 俊、山口 理恵、豊田 圭亮、茅野貴秋、大熊康修、野村靖幸、小澤 光一郎
    • Organizer
      第38回 日本脳科学会
    • Place of Presentation
      沖縄県那覇市
    • Related Report
      2012 Final Research Report
  • [Presentation] MyD88欠損による新規糖尿病発症メカニズムの解明2011

    • Author(s)
      横山 匠太、細井 徹、松尾 俊、審良 静男、小澤 光一郎
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Related Report
      2012 Final Research Report
  • [Presentation] 新機構肥満薬における作用機構の解明2011

    • Author(s)
      馬場 幸子、細井 徹、松尾 俊、山口理恵、豊田圭亮、小澤 光一郎
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] 肥満脳におけるレプチン受容体応答系抑制機構の解明と創薬:小胞体ストレスの関与2011

    • Author(s)
      細井徹
    • Organizer
      第38回日本脳科学会
    • Place of Presentation
      沖縄県那覇市
    • Related Report
      2011 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
    • Related Report
      2010 Annual Research Report
  • [Presentation] 感染及び拘束ストレスにより誘発される摂食抑制のメカニズムの解明-視床下部 MyD88/STAT3 経路の関わり-2010

    • Author(s)
      木村 仁美、山脇 洋輔、細井 徹、小澤 光一郎
    • Organizer
      第118回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2010-11-19
    • Related Report
      2012 Final Research Report
  • [Presentation] 神田 稔子, 細井 徹, 石口 瑞穂, 小澤 光一郎2010

    • Author(s)
      神田 稔子, 細井 徹, 石口 瑞穂, 小澤 光一郎
    • Organizer
      第118回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2010-11-19
    • Related Report
      2012 Final Research Report
  • [Presentation] 小胞体ストレスを標的とした肥満治療薬の解明2010

    • Author(s)
      馬場 幸子、細井 徹、松尾 俊、山口理恵、豊田圭亮、小澤 光一郎
    • Organizer
      118回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2010-11-19
    • Related Report
      2012 Final Research Report
  • [Presentation] 小胞体ストレスを標的とした肥満治療薬の解明2010

    • Author(s)
      馬場幸子
    • Organizer
      第118回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2010-11-19
    • Related Report
      2010 Annual Research Report
  • [Book] 薬と疾病II.薬物治療(1)2012

    • Author(s)
      赤池昭紀
    • Total Pages
      440
    • Publisher
      東京化学同人
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2012 Final Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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