Unraveling and exploitation of novel metabolic system regulated by a metabolite sensor
| Project/Area Number |
20K08855
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 代謝産物センサー / 肥満 / メタボリックシンドローム / NADH / 脂肪酸CoA / 代謝産物 / 脂肪酸 / ジヌクレオチド / センサー / 小分子化合物 |
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| Outline of Research at the Start |
代謝産物によって活性が調節され、かつその活性が様々な代謝経路の遺伝子発現を調節する代謝産物センサー分子を同定した。同分子は肥満病態で不活性化されており、その活性化が新しい代謝疾患治療薬となり得る知見を得た。
これに基づいて同分子を活性化する小分子化合物をスクリーニング、ヒット化合物を得た。実臨床に応用するにはさらなる構造改変などを通じて活性を強力にするなどの工夫が必要で、同分子の分子基盤をさらに明らかにしつつ、本邦発の新しくかつ有効な治療薬の創出をめざす。
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| Outline of Final Research Achievements |
We have investigated the metabolic systems regulated by a metabolite sensor that we identified recently. While we unraveled the roles of the metabolite sensor in multiple tissues, we were able to publish a paper regarding the liver biology, and several papers are now in revision. In addition, more findings are almost ready to be submitted. Those findings significantly accelerate our understanding the molecular basis of obesity.
Apart from this, we also identified a novel role of this molecule, that offers translational opportunites as well and paves the way to provide multidisciplinary angles. This aspect of our reserach could be a groundbreaking discovery in multiple fields.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は従来になかった新しい代謝疾患の病態の考え方をもたらし、かつ治療応用性といった医療応用性につながるものであり、社会実装の可能性が高い。また同時に見出した新しい分子基盤もやはり社会実装性が高い。これらはこの数年の間といったごく近未来に臨床応用が期待される。代謝は狭義の代謝疾患にとどまらず、幅広い生物学の基盤となっているため、領域横断的な理解、医療応用に発展する可能性が高い。
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Report
(2 results)
Research Products
(7 results)
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[Journal Article] A case of early-onset diabetes with impaired insulin secretion carrying a PAX6 gene Gln135* mutation2022
Author(s)
Motohiro Sekiya 1, Mikiko Yuhara 1, Yuki Murayama 1, Mariko Ohyama Osawa 1, Rikako Nakajima 1, Nami Ohuchi 1, Nako Matsumoto 1, Daichi Yamazaki 1, Sayuri Mori 1, Takaaki Matsuda 1, Yoko Sugano 1, Yoshinori Osaki 1, Hitoshi Iwasaki 1, Hiroaki Suzuki 1, Hitoshi Shimano 1
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Journal Title
Endocrinol Diabetes Metab Case Rep .
Volume: Aug 1
Pages: 22-0271
DOI
Related Report
Peer Reviewed
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