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Elucidation of the control mechanism of GLP-1/incretin signaling by non-nutritional food molecules.

Research Project

Project/Area Number 20K05927
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionSaga University

Principal Investigator

Mitsutake Susumu  佐賀大学, 農学部, 准教授 (10344475)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsGPR120 / GLP-1 / phytosphingosine / teadenol A / isofloridoside / incretin / FFAR4 / phytosphingosie / teadenol / T1R2/T1R3 / インクレチン / sphingomyelin
Outline of Research at the Start

長鎖脂肪酸受容体GPR120は、小腸上皮内分泌L細胞に発現し、その活性化は消化管ホルモンであるインクレチンGLP-1の分泌を促進させます。GLP-1は、インスリンの分泌促進、食欲抑制等に働くことが知られ、2型糖尿病の改善/予防に有効である事が知られています。私は近年、酵母の細胞膜に含まれるスフィンゴ脂質の一つphytosphingosine(PHS)が、GPR120を活性化する事を見出しました。私は本研究で、PHSや他の食品成分によるGPR120の活性制御機構を詳細に解析し、「非栄養性食品分子のGPR120を介した新しい食品機能」を確立したいと考えています。

Outline of Final Research Achievements

Recently, I found that phytosphingosine (PHS), one of the sphingolipids contained in the plasmamembrane of yeast, is a novel ligand for GPR120 and induces the secretion of GLP-1, one of the incretins. GLP-1 is known to induce anti-diabetes/anti-obesity, and PHS was an interesting molecule that promotes GLP-1 secretion in non-nutritive manner. I believe that such molecules still exist in foods. In this research, I found that teadenol A, contained in microbially fermented tea, and isofloridoside, contained in seaweed, stimulate the secretion of GLP-1 from mouse endocrine cells. Additionally, I also revealed that PHS binds to GPR120 in a region distinct from other ligands.

Academic Significance and Societal Importance of the Research Achievements

インクレチンの一つGLP-1は、インスリンの分泌や食欲の抑制を介して抗メタボリック症候群に働き、2型糖尿病の創薬ターゲットとして注目を集めている。私は本研究でPHS以外にも、teadenol Aとisofloridosideが小腸内分泌細胞からGLP-1の分泌を誘導する事を明らかにした。GLP-1やインクレチンシグナリングは、元来、エネルギーの過剰摂取を防ぐためのフィードバックシステムであるが、私が見出した3つの分子は、何も非栄養的にこのシステムを活性化させる。私の発見は、食品中の非栄養分子の新たな食品機能の存在を示唆しており大変興味深い。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2022 2021 2020

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Red algae-derived isofloridoside activates the sweet taste receptor T1R2/T1R32022

    • Author(s)
      M. Akishino, Y. Aoki, H. Baba, M. Asakawa, Y. Hama, S. Mitsutake
    • Journal Title

      Food Bioscience

      Volume: 50 Pages: 102186-102186

    • DOI

      10.1016/j.fbio.2022.102186

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The molecular mechanism of phytosphingosine binding to FFAR4/GPR120 differs from that of other fatty acids2021

    • Author(s)
      Nagasawa Tomotaka、Horitani Masaki、Kawaguchi Shin‐ichi、Higashiyama Shigeki、Hama Yoichiro、Mitsutake Susumu
    • Journal Title

      FEBS Open Bio

      Volume: 11 Issue: 11 Pages: 3081-3089

    • DOI

      10.1002/2211-5463.13301

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liberation of eicosapentaenoic acid and degradation of the major cell wall polysaccharide porphyran by fermentation of nori, the dried thalli of Pyropia yezoensis, with koji2021

    • Author(s)
      Hama Yoichiro、Yamagata Emi、Takahama Noriko、Yoshimura Yuka、Yanagida Rin、Mitsutake Susumu
    • Journal Title

      Journal of Applied Phycology

      Volume: 33 Issue: 6 Pages: 4105-4111

    • DOI

      10.1007/s10811-021-02590-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Teadenol A in microbial fermented tea acts as a novel ligand on GPR120 to increase GLP-1 secretion2020

    • Author(s)
      Tomotaka Nagasawa , Kanji Ishimaru, Shigeki Higashiyama, Yoichiro Hama, Susumu Mitsutake
    • Journal Title

      Food & Function

      Volume: 11 Issue: 12 Pages: 10534-10541

    • DOI

      10.1039/d0fo02442b

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Phytosphingosine is a novel ligand of GPR120/FFAR42021

    • Author(s)
      Susumu Mitsutake
    • Organizer
      2021 BLIRC/KSMCB-Division of Lipid Biology Joint Symposium, Seoul
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 微生物発酵茶に含まれるTeadenol AはGPR120に作用しGLP-1の分泌を誘導する2020

    • Author(s)
      長澤智隆、石丸幹二、東山繁樹、濱 洋一郎、光武 進
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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