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Physiological role of free fatty acid receptor GPR120.

Research Project

Project/Area Number 21390021
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKyoto University

Principal Investigator

HIRASAWA Akira  京都大学, 大学院・薬学研究科, 准教授 (70242633)

Co-Investigator(Renkei-kenkyūsha) AWAJI Takeo  埼玉医科大学, 医学部, 講師 (60297546)
KOSHIMIZU Taka-aki  自治医科大学, 医学研究科, 准教授 (20392491)
LIU Ning  京都大学, 大学院・薬学研究科, 研究員 (70464196)
IIDA Keiko  京都大学, 大学院・薬学研究科, 教務補佐 (00422999)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2011: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2009: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywords薬理学 / GPCR / GPR120 / フローサイトメーター / ゲノム創薬科学
Research Abstract

Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. We showed that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. In human, we identified a deleterious non-synonymous mutation(p. R270H) that inhibits GPR120 signalling activity. Furthermore, the p. R270H variant increases the risk of obesity in European populations. We conclude that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (28 results)

All 2012 2011 2010 2009 Other

All Journal Article (13 results) (of which Peer Reviewed: 12 results) Presentation (12 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human2012

    • Author(s)
      Ichimura A
    • Journal Title

      Nature

      Volume: 483 Issue: 7389 Pages: 350-354

    • DOI

      10.1038/nature10798

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor2011

    • Author(s)
      Kimura I, Inoue D, Hirasawa A, et al
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 108(19) Issue: 19 Pages: 8030-8035

    • DOI

      10.1073/pnas.1016088108

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders2011

    • Author(s)
      Hara T, Hirasawa A, et al
    • Journal Title

      J Pharm Sci

      Volume: 100(9) Issue: 9 Pages: 3594-3601

    • DOI

      10.1002/jps.22639

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure-Activity Relationships of GPR120 Agonists Based on a Docking Simulation2010

    • Author(s)
      Sun Q, Hirasawa A, et al
    • Journal Title

      Mol Pharmacol

      Volume: 78(5) Issue: 5 Pages: 804-810

    • DOI

      10.1124/mol.110.066324

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] New Frontiers in Gut Nutrient Sensor Research: Free Fatty Acid Sensing in the Gastrointestinal Tract2010

    • Author(s)
      Miyauchi S, Hirasawa A, et al
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 112 Issue: 1 Pages: 19-24

    • DOI

      10.1254/jphs.09R09FM

    • NAID

      10027908410

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure-Activity Relationships of GPR120 Agonists Based on a Docking Simulation.2010

    • Author(s)
      Sun Q, Hirasawa A, Hara T, 他
    • Journal Title

      Mol Pharmacol

      Volume: 78 Pages: 804-810

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Free fatty acid sensing in the gastrointestinal tract2010

    • Author(s)
      Miyauchi S, Hirasawa A, 他
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 112(1) Pages: 19-24

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 脂肪酸受容体に対するリガンド探索,生理機能の解明と創薬応用2010

    • Author(s)
      平澤明、辻本豪三
    • Journal Title

      医学のあゆみ

      Volume: vol.233, no.9 Pages: 755-760

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Novel selective ligands for free fatty acid receptors GPR120 and GPR402009

    • Author(s)
      Hara T, Hirasawa A, et al
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol

      Volume: 380(3) Issue: 3 Pages: 247-255

    • DOI

      10.1007/s00210-009-0425-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Free fatty acid receptors act as nutrient sensors to regulate energy homeostasis2009

    • Author(s)
      Ichimura A, Hirasawa A, et al
    • Journal Title

      Prostaglandins & Other Lipid Mediators

      Volume: 89 Issue: 3-4 Pages: 82-88

    • DOI

      10.1016/j.prostaglandins.2009.05.003

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Distribution and regulation of protein expression of the free fatty acid receptor GPR1202009

    • Author(s)
      宮内諭
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol 379(4)

      Pages: 427-434

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel selective ligands for free fatty acid receptors GPR120 and GPR402009

    • Author(s)
      原貴史
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol 380(3)

      Pages: 247-255

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Flow cytometry-based binding assay for GPR40 (FFAR1 ; free fatty acid receptor 1)2009

    • Author(s)
      原貴史
    • Journal Title

      Mol Pharmacol 75(1)

      Pages: 85-91

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 長鎖脂肪酸受容体GPR120の生理機能の解明と創薬応用2012

    • Author(s)
      平澤明、辻本豪三
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      際会議場(愛知県)
    • Year and Date
      2012-04-19
    • Related Report
      2011 Final Research Report
  • [Presentation] 薬物スクリーニングへのイメージング技術の応用2012

    • Author(s)
      平澤明、辻本豪三、原貴史
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学キャンパス(北海道)
    • Year and Date
      2012-03-30
    • Related Report
      2011 Final Research Report
  • [Presentation] 薬物スクリーニングへのイメージング技術の応用2012

    • Author(s)
      平澤明、辻本豪三、原貴史
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学キャンパス内(北海道)
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] ドッキングシミュレーションに基づくGPR40アゴニストの構造活性相関2012

    • Author(s)
      Takeuchi M, Hirasawa A, Hara T, Hirano T, Suzuki T, Miyata N, Ishiguro M, Tsujimoto G
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学キャンパス内(北海道)
    • Year and Date
      2012-03-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] 脂肪酸受容体GPR120の構造活性相関と薬理学的機能解析2012

    • Author(s)
      原貴史、平澤明、竹内理人、鮎川久美子、白井遼平、辻本豪三
    • Organizer
      第41回日本心脈管作動物質学会
    • Place of Presentation
      秋田キャッスルホテル(秋田県)
    • Year and Date
      2012-02-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Structure-Activity Relationships of GPR120 Agonists Based on a Docking Simulation2011

    • Author(s)
      平澤明
    • Organizer
      AIMECS11 ; Frontier of Medicinal Science
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2011-11-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Structure-activity relationships of GPR40 agonists based on a docking simulation2011

    • Author(s)
      Takeuchi M, Sun Q, Hara T, Hirasawa A, Ishiguro M, Suzuki T, Miyata N, Tsujimoto G.
    • Organizer
      第6回国際受容体シンポジウム
    • Place of Presentation
      京都大学(京都府)
    • Year and Date
      2011-04-02
    • Related Report
      2011 Final Research Report
  • [Presentation] GPR120 mediates high-fat diet-induced adipocyte hypertrophy and obesity2010

    • Author(s)
      Ichimura A, Akira H, 他
    • Organizer
      16th World Congress of Basic and Clinical Pharmacology
    • Place of Presentation
      コペンハーゲン、デンマーク
    • Year and Date
      2010-07-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 脂肪酸受容体GPR120の代謝調節機構の解析2010

    • Author(s)
      平澤明、原貴史、市村敦彦、宮内諭、木村郁夫、輿水崇鏡、辻本豪三
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2010-03-16
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂肪酸受容体GPR120の代謝調節機構の解析2010

    • Author(s)
      平澤明
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-03-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 糖尿病と脂肪酸受容体ファミリー2009

    • Author(s)
      平澤明、辻本豪三
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      国立京都国際会議場(京都府)
    • Year and Date
      2009-03-26
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂肪酸受容体ノックアウトマウスによる代謝疾患解析2009

    • Author(s)
      平澤明、辻本豪三
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-03-18
    • Related Report
      2011 Final Research Report
  • [Remarks] 脂肪センサーGPR120が食事性肥満の原因遺伝子であることの発見、2012年2月20日

    • URL

      http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2011/120220_1.htm

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://gdds.pharm.kyoto-u.ac.jp/

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] G蛋白質共役型レセプター作動剤2011

    • Inventor(s)
      辻本豪三、平澤明, 他
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Number
      2011-016446
    • Filing Date
      2011-01-28
    • Related Report
      2010 Annual Research Report

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

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