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Search for New Appetite and Fat Accumulation Regulators and Functional Analysis Based on Rho Kinase

Research Project

Project/Area Number 16K09818
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Yoshida Morikatsu  国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (70393212)

Co-Investigator(Kenkyū-buntansha) 宮里 幹也  国立研究開発法人国立循環器病研究センター, 研究所, 部長 (50291183)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords生理活性ペプチド / Rhoキナーゼ / オーファンGPCR / 摂食・エネルギー代謝 / 内分泌
Outline of Final Research Achievements

In this study, we focused on the activation pathway of Rho-kinase (ROCK) by G protein-coupled receptors (GPCR) to identify unknown bioactive peptides that regulate food intake, energy metabolism, and glycolipid metabolism, and searched for novel ROCK activators as GPCR ligands. Although no new peptides were identified, strong agonist activity against GPCR-Y was successfully detected. In addition, functional analysis of GPCR-X, whose intracellular signaling pathway was not clear, was advanced. GPCR-X was shown to have, by agonist binding, not only intracellular calcium increasing activity via G alpha q, but also transcriptional activity of serum response factors via G alpha 13 and ROCK activation.

Academic Significance and Societal Importance of the Research Achievements

近年の肥満症や糖尿病、摂食障害患者の急増に伴い、摂食及び代謝調節ペプチドを中心とした内分泌学・代謝学研究は世界中の研究グループにより精力的に進められている。また、医薬品の作用標的の多くはGPCRであり、リガンド不明なGPCRに対する内因性リガンド探索は新たな作用機序を有する医薬品(作動薬、拮抗薬)の開発において重要である。本研究のようなGPCRのクロストークによる、インスリン及びレプチン抵抗性の解除を目指した治療戦略は、肥満症や糖尿病、摂食障害等に対する新薬開発の新しいアプローチに繋がるものとして期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Invited: 2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Conformational Change in the Ligand-Binding Pocket via a KISS1R Mutation (P147L) Leads to Isolated Gonadotropin-Releasing Hormone Deficiency2017

    • Author(s)
      Shimizu Koichiro、Yonekawa Tadato、Yoshida Morikatsu、Miyazato Mikiya、Miura Ayako、Sakoda Hideyuki、Yamaguchi Hideki、Nakazato Masamitsu
    • Journal Title

      Journal of the Endocrine Society

      Volume: 1 Issue: 10 Pages: 1259-1271

    • DOI

      10.1210/js.2017-00277

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Luqin-like RYamide peptides regulate food-evoked responses in C. elegans2017

    • Author(s)
      Ohno H, Yoshida M, Sato T, Kato J, Miyazato M, Kojima M, Ida T, Iino Y
    • Journal Title

      Elife

      Volume: 6. pii Pages: 1-23

    • DOI

      10.7554/elife.28877

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] m7325 is MyoD-dependently expressed in activated muscle satellite cells.2017

    • Author(s)
      Takei D, Nishi M, Fukada S, Doi M, Okamura H, Uezumi A, Zhang L, Yoshida M, Miyazato M, Ichimura A, Takeshima H.
    • Journal Title

      Biomed Res.

      Volume: 38 Pages: 215-219

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Purification and characterization of bioactive peptides RYamide and CCHamide in the kuruma shrimp Marsupenaeus japonicus2017

    • Author(s)
      Mekata T, Kono T, Satoh J, Yoshida M, Mori K, Sato T, Miyazato M, Ida T*
    • Journal Title

      Gen Comp Endocrinol

      Volume: 246 Pages: 321-330

    • DOI

      10.1016/j.ygcen.2017.01.008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 低親和性ニューロテンシン受容体の細胞内情報伝達機構の解析2019

    • Author(s)
      吉田守克、寒川賢治、宮里幹也
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] RYamideペプチドの新展開2017

    • Author(s)
      井田 隆徳、大野 速雄、吉田 守克、佐藤 貴弘、加藤 丈治、宮里 幹也、 児島 将康、飯野 雄一
    • Organizer
      第14回GPCR研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] CeRYamides, members of the conserved RYamide peptide family, mediate food responses after fasting in C. elegans2017

    • Author(s)
      Hayao Ohno, Morikatsu Yoshida, Takahiro Sato, Johji Kato, Mikiya Miyazato, Masayasu Kojima, Takanori Ida & Yuichi Iino
    • Organizer
      16th TOKYO IGAKUKEN International Symposium
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 新規生理活性ペプチドを探索するための新たな活性検出系の構築2016

    • Author(s)
      中里祐毅、吉田守克、井上飛鳥、青木淳賢、中里雅光、宮里幹也
    • Organizer
      第7回 ペプチド・ホルモン研究会
    • Place of Presentation
      久留米ホテル エスプリ
    • Year and Date
      2016-09-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 新規KISS1受容体変異(P147L)による性腺機能低下症の機能解析2016

    • Author(s)
      清水浩一郎、米川忠人、迫田秀之、吉田守克、宮里幹也、中里雅光
    • Organizer
      第13回 GPCR研究会
    • Place of Presentation
      日本科学未来館
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 新規キスペプチン受容体変異(Pro147Leu)による思春期欠損症の機能解析2016

    • Author(s)
      山口秀樹、米川忠人、清水浩一郎、迫田秀之、吉田守克、宮里幹也、中里雅光
    • Organizer
      第89回 日本内分泌学会学術総会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Book] ペプチド医薬品のスクリーニング・安定化・製剤化技術2018

    • Author(s)
      吉田 守克,宮里 幹也
    • Total Pages
      7
    • Publisher
      情報技術協会
    • Related Report
      2017 Research-status Report
  • [Remarks]

    • URL

      http://www.ncvc.go.jp/res/divisions/biochemistry/

    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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