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食欲調節作用を有する低分子ペプチドの探索と作用機構の解析

Research Project

Project/Area Number 18780095
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Food science
Research InstitutionKyoto University

Principal Investigator

大日向 耕作  Kyoto University, 農学研究科, 准教授 (00361147)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywords食欲調節 / 視床下部 / プロスタグランジンD2 / DP1受容体 / プロスタグランジンE2 / EP4 / アンジオテンシンAT受容体 / 脳 / 低分子ペプチド / 補体C3a / アンジオテンシンAT2受容体 / コレシストキニン / グレリン受容体
Research Abstract

食欲調節におけるプロスタグランジン(PG)類の役割を明らかにするため、飢餓状態における視床下部PG合成酵素の発現量の変化を測定し、リポカリン型PGD2合成酵素の発現量が上昇することを見出した。PGD2がDP1受容体を介して摂食促進作用を示すとともに、DP1受容体を阻害することにより摂食量、体重、脂肪量が著しく低下することから、PGD2はエネルギー不足状態で活性化される新しい摂食促進因子であり、食欲調節に重要な役割を演じていることがわかった。
一方、PGD2の構造異性体であるPGE2はEP4受容体を介して摂食抑制作用を示すが、angiotensin AT2アゴニストのnovokininが、本経路を活性化する経口投与で有効な摂食抑制ペプチドであることを明らかにした。また、中枢神経系にも存在するangiotensin IIがAT2受容体の下流でPGE2-EP4経路を活性化し、摂食抑制作用を示すことも明らかにした。
菜種タンパク質由来の摂食抑制ペプチドArg-Ile-TyrがCCK分泌能を有することをSTC-1細胞を用いて明らかにした。また、本ペプチドは動脈弛緩作用ならびに血圧降下作用を有するが、動脈弛緩作用がコレシストキニン(CCK)放出を介することを明らかにした。これはCCK自身が動脈弛緩・血圧降下作用を有することを示唆する重要な実験結果である。
なお、大豆タンパク質由来のグレリンアゴニストペプチドを探索したが、新規ペプチドの同定には至っていない。現在検討中である。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (14 results)

All 2008 2007 2006

All Journal Article (11 results) (of which Peer Reviewed: 7 results) Presentation (3 results)

  • [Journal Article] Angiotensin II and III suppress food intake via angiotensin AT2 receptor and prostaglandin EP4 receptor2008

    • Author(s)
      Ohinata K, Fujiwara Y, Fukumoto S, Iwai M, Horiuchi M, Yoshikawa
    • Journal Title

      FEBS Lett 582(5)

      Pages: 773-777

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Central prostaglandin D(2) stimulates food intake via the neuropeptide Y system in mice2008

    • Author(s)
      Ohinata K, Takagi K, Biyajima K, Fujiwara Y, Fukumoto S, Eguchi N,
    • Journal Title

      FEBS Lett 582(5)

      Pages: 679-684

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rubimetide (Met-Arg-Trp) derived from Rubisco exhibits anxiolytic-like activity via the DP1 receptor in male2008

    • Author(s)
      Zhao H, Ohinata K, Yoshikawa M.
    • Journal Title

      Peptides 24(4)

      Pages: 629-632

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Soymorphins, novel mu opioid peptides derived from soy beta-conglycinin beta-subunit, have anxiolytic2007

    • Author(s)
      Ohinata K, Agui S, Yoshikawa M.
    • Journal Title

      Biosci Biotechnol Biochem 71(10)

      Pages: 2618-2621

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Rubiscolin-6, a delta opioid peptide derived from spinach Rubisco, has anxiolytic effect via activating2007

    • Author(s)
      Hirata H, Sonoda S, Agui S, Yoshida M, Ohinata K, Yoshikawa
    • Journal Title

      Peptides 28(10)

      Pages: 1998-2003

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] beta-Lactotensin, a neurotensin agonist peptide derived from bovine beta-lactoglobulin, enhances memory2007

    • Author(s)
      Ohinata K, Sonoda S, Inoue N, Yamauchi R, Wada K, Yoshikawa M.
    • Journal Title

      Peptides 28(7)

      Pages: 1470-1474

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of food intake by a complement C3a agonist [Trp5]-oryzatensin(5-9)2007

    • Author(s)
      Ohinata K, Suetsugu K, Fujiwara Y, Yoshikawa M.
    • Journal Title

      Peptides 28(3)

      Pages: 602-606

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enterostatin (APGPR) enhances memory consolidation in mice2007

    • Author(s)
      Ohinata K, Sonoda S, Shimano T, Yoshikawa M.
    • Journal Title

      Peptides 28(3)

      Pages: 719-721

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of prostaglandin E receptor EP4 subtype suppresses food intake in mice2006

    • Author(s)
      Ohinata K, Suetsugu K, Fujiwara Y, Yoshikawa M
    • Journal Title

      Prostaglandins Other Lipid Mediat. 81(1-2)

      Pages: 31-36

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Arg-Ile-Tyr (RIY) derived from rapeseed protein decreases food intake and gastric emptying after oral administration in mice2006

    • Author(s)
      Marczak ED, Ohinata K, Lipkowski AW, Yoshikawa M
    • Journal Title

      Peptides

      Pages: 2065-2068

    • Related Report
      2006 Annual Research Report
  • [Journal Article] [Trp3, Arg5]-ghrelin(1-5) stimulates growth hormone secretion and food intake via growth hormone secretagogue (GHS) receptor2006

    • Author(s)
      Ohinata K, Kobayashi K, Yoshikawa M
    • Journal Title

      Peptides 27(7)

      Pages: 1632-1637

    • Related Report
      2006 Annual Research Report
  • [Presentation] Prostaglandin D2 stimulates food intake through the NPY-dependent mechanism2008

    • Author(s)
      Ohinata K, Yoshikawa M
    • Organizer
      The 9th Neuropeptide Y International Meeting
    • Place of Presentation
      沖縄、かりゆしビーチリゾートオシャンスパ
    • Year and Date
      2008-03-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Elongation of anti-hypertensive effect of tea catechin by co-administration with milk protein in spontaneously2007

    • Author(s)
      Ohinata K, Yoshikawa M
    • Organizer
      The International Conference on Food Factors for Health Promotion (ICOFF2007)
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2007-11-30
    • Related Report
      2007 Annual Research Report
  • [Presentation] Mechanism for stimulation of food intake by complement C5a2007

    • Author(s)
      Ohinata K, Yoshikawa M
    • Organizer
      4th International Workshop on Complement Associated Diseases, Animal Models, and
    • Place of Presentation
      ギリシャ、Port Heli
    • Year and Date
      2007-06-11
    • Related Report
      2007 Annual Research Report

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

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