Physiological functions of branched-chain amino acids as regulatory factors in mammals
| Project/Area Number |
17H03817
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Food science
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| Research Institution | Chubu University (2019)
Nagoya University (2017-2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北浦 靖之 名古屋大学, 生命農学研究科, 講師 (90442954)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
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| Keywords | BCAA / BCKDH / BDK / mTORC1 / 骨格筋 / 脳神経 / マウス / 筋肉 / 分岐鎖アミノ酸 / 代謝調節 / コンディショナルノックアウト |
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| Outline of Final Research Achievements |
Branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) have drawn attention as metabolic regulators in cells due to the diverse physiological actions. In the present study, we elucidated the mechanism that branched-chain α-keto acid dehydrogenase kinase (BDK), a regulator of BCAA metabolism, is controlled by Ca ions in cells. In the studies using conditional BDK-KO mice, we demonstrated that chronically low levels of BCAAs in skeletal muscle resulted in enhanced reactivity of muscle mTORC1, and slow recovery of muscle glycogen after exercise. Furthermore, we suggested that chronically low levels of BCAAs in brain were responsible for neurological abnormality.
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| Academic Significance and Societal Importance of the Research Achievements |
分岐鎖アミノ酸(BCAA)の代謝調節機構はBCAAの生理作用のメカニズムを解明する上で重要である。本研究において、CaイオンによってBCAA代謝が調節されることを証明したが、この機構はBCAA代謝の新たな調節機構であり、これにより運動などによる骨格筋BCAA代謝の亢進を説明できる。コンディショナルBDK欠損マウスを用いた研究により、骨格筋のタンパク質およびグリコーゲン代謝においてBCAAが深く関与していることを示唆するとともに、正常な脳機能を維持するためには十分なBCAAの供給が重要であることを証明した。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex.2018
Author(s)
Liang Weng , Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice2017
Author(s)
Honda T, Ishigami M, Luo F, Lingyun M, Ishizu Y, Kuzuya T, Hayashi K, Nakano I, Ishikawa T, Feng GG, Katano Y, Kohama T, Kitaura Y, Shimomura Y, Goto H, Hirooka Y.
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Journal Title
Metabolism Clinical And Experimental.
Volume: 69
Pages: 177-187
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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