Study on the mechanism of regulation of mitochondrial function by brain-derived neurotrophic factor
Project/Area Number |
18H03187
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 59040:Nutrition science and health science-related
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Research Institution | Kyushu University (2020) Hokkaido University (2018-2019) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
福島 新 北海道大学, 医学研究院, 客員研究員 (40706553)
横田 卓 北海道大学, 大学病院, 特任講師 (90374321)
高田 真吾 北海道大学, 医学研究院, 博士研究員 (60722329)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2019: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2018: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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Keywords | 脳由来神経栄養因子 / マイオカイン / 骨格筋 / ミトコンドリア |
Outline of Final Research Achievements |
We clarified that brain-derived neurotrophic factor (BDNF) is a myokine secreted from skeletal muscle cells, and found that it is present in mitochondria in skeletal muscle cells. We found that BDNF plays an important role in regulating the amount and function of skeletal muscle mitochondria, especially in fatty acid oxidation. Furthermore, these effects of BDNF were mediated by AMPKα and PGC-1α signals. Administration of human recombinant BDNF to post-myocardial infarction heart failure model mice increased skeletal muscle BDNF, improved AMPKα-PGC-1α signal, and improved endurance exercise capacity. The therapeutic effect of BDNF was equivalent to that of exercise therapy, and was mediated by the same signal.
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Academic Significance and Societal Importance of the Research Achievements |
骨格筋は人体最大の臓器であり、生体の代謝の中心である。骨格筋はこれまで運動器として考えられていたが、種々のホルモンを分泌する内分泌器官と考えられるようになった。心不全を始めとする慢性疾患において、種々の骨格筋異常が出現し、生活の質だけでなく生命予後を規定することが知られている。骨格筋をターゲットとした治療法は運動療法があるが、高齢者ではその遂行が困難であったり、効果が不十分であったりで、新たな治療法が求められている。本研究はマイオカインであるBDNFが運動療法代替治療法となり得ることを示し、今後の臨床応用へ向けた研究が期待される。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Brain-derived neurotrophic factor improves impaired fatty acid oxidation via the activation of AMPKα-PGC1α signaling in skeletal muscle of mice with heart failure2021
Author(s)
125.Matsumoto J, Takada S, Furihata T, Nambu H, Kakutani N, Maekawa S, Mizushima W, Nakano I, Fukushima A, Yokota T, Tanaka S, Handa H, Sabe H, Kinugawa S
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Journal Title
Circ Heart Fail
Volume: 14
Related Report
Peer Reviewed
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[Journal Article] Inhibition of xanthine oxidase in the acute phase of myocardial infarction prevents skeletal muscle abnormalities and exercise intolerance2021
Author(s)
124.Nambu H, Takada S, Maekawa S, Matsumoto J, Kakutani N, Furihata T, Shirakawa R, Katayama T, Nakajima T, Yamanashi K, Obata Y, Nakano I, Tsuda M, Saito A, Fukushima A, Yokota T, Nio-Kobayashi J, Yasui H, Higashikawa K, Kuge Y, Anzai T, Sabe H, Kinugawa S
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Journal Title
Cardiovasc Res
Volume: 117
Pages: 805-819
Related Report
Peer Reviewed
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[Journal Article] Cardiac-specific loss of mitoNEET expression is linked with age-related heart failure2021
Author(s)
126.Furihata T, Takada S, Kakutani N, Maekawa S, Tsuda M, Matsumoto J, Mizushima W, Fukushima A, Yokota T, Enzan N, Matsushima S, Handa H, Fumoto Y, Nio-Kobayashi J, Iwanaga T, Tanaka S, Tsutsui H, Sabe H, Kinugawa S
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Journal Title
Commun Biol
Volume: 4
Pages: 138-138
Related Report
Peer Reviewed / Open Access
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[Journal Article] Angiotensin-converting-enzym inhibitor prevents skeletal uscle fibrosis in myocardial infarction mice2020
Author(s)
121.Yamanashi K, Kinugawa S, Fukushima A, Kakutani N, Takada S, Obata Y, Nakano I, Yokota T, Kitaura Y, Shimomura Y, Anzai T
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Journal Title
Life Sciences
Volume: 250
Pages: 117593-117593
Related Report
Peer Reviewed
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[Journal Article] Impaired mitochondrial oxidative phosphorylation capacity in epicardial adipose tissue is associated with decreased concentration of adiponectin and severity of coronary atherosclerosis.2019
Author(s)
Nakajima T, Yokota T, Shingu Y, Yamada A, Iba Y, Ujihira K, Wakasa S, Ooka T, Takada S, Shirakawa R, Katayama T, Furihata T, Fukushima A, Matsuoka R, Nishihara H, Dela F, Nakanishi K, Matsui Y, Kinugawa S.
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Journal Title
Sci Rep
Volume: 9
Issue: 1
Pages: 3535-3535
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Increased echo intensity of skeletal muscle is associated with exercise intolerance in patients with heart failure2019
Author(s)
Nakano I, Hori H, Fukushima A, Yokota T, Kinugawa S, Takada S, Yamanashi K, Obata Y, Kitaura Y, Kakutani N, Abe T, Anzai T
Organizer
Euro Prevent 2019
Related Report
Int'l Joint Research
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[Presentation] Administration of brain-derived neurotrophic factor improves the lowered exercise capacity and mitochondrial function in the skeletal muscle of mice with post-infarct heart failure.2018
Author(s)
Takada S, Matsumoto J, Kinugawa S, Furihata T, Nambu H, Kakutani N, Maekawa S, Shirakawa R, Katayama T, Yamanashi K, Obata Y, Saito A, Fukushima A, Yokota T, Okita K, Anzai T
Organizer
American Heart Association Scientific Session 2018
Related Report
Int'l Joint Research
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