Search for New Appetite and Fat Accumulation Regulators and Functional Analysis Based on Rho Kinase
| Project/Area Number |
16K09818
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | National Cardiovascular Center Research Institute |
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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)
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| 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)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(12 results)
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[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.
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Journal Title
Biomed Res.
Volume: 38
Pages: 215-219
Related Report
Peer Reviewed / Open Access
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