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Study on the mechanism of regulation of mitochondrial function by brain-derived neurotrophic factor

Research Project

Project/Area Number 18H03187
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionKyushu University (2020)
Hokkaido University (2018-2019)

Principal Investigator

Kinugawa Shintaro  九州大学, 医学研究院, 准教授 (60399871)

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)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
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)
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.

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。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (19 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 7 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

  • [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
    • Journal Title

      Circ Heart Fail

      Volume: 14

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      Cardiovasc Res

      Volume: 117 Pages: 805-819

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      Commun Biol

      Volume: 4 Pages: 138-138

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiotensin-converting-enzym inhibitor prevents skeletal uscle fibrosis in myocardial infarction mice2020

    • Author(s)
      122.Kakutani N, Takada S, Nambu H, Matsumoto J, Furihata T, Yokota T, Fukushima A, Kinugawa S
    • Journal Title

      Skelet Muscle

      Volume: 10 Pages: 11-11

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      Life Sciences

      Volume: 250 Pages: 117593-117593

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 3535-3535

    • DOI

      10.1038/s41598-019-40419-7

    • NAID

      120006603703

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A mitochondrial delivery system using liposome-based nanocarriers that target myoblast cells2019

    • Author(s)
      Katayama Takashi、Kinugawa Shintaro、Takada Shingo、Furihata Takaaki、Fukushima Arata、Yokota Takashi、Anzai Toshihisa、Hibino Mitsue、Harashima Hideyoshi、Yamada Yuma
    • Journal Title

      Mitochondrion

      Volume: 49 Pages: 66-72

    • DOI

      10.1016/j.mito.2019.07.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients2019

    • Author(s)
      Shirakawa Ryosuke、Yokota Takashi、Nakajima Takayuki、Takada Shingo、Yamane Miwako、Furihata Takaaki、Maekawa Satoshi、Nambu Hideo、Katayama Takashi、Fukushima Arata、Saito Akimichi、Ishimori Naoki、Dela Flemming、Kinugawa Shintaro、Anzai Toshihisa
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 14709-14709

    • DOI

      10.1038/s41598-019-51298-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Linoleic acid improves assembly of the CII subunit and CIII2/CIV complex of the mitochondrial oxidative phosphorylation system in heart failure2019

    • Author(s)
      Maekawa Satoshi、Takada Shingo、Nambu Hideo、Furihata Takaaki、Kakutani Naoya、Setoyama Daiki、Ueyanagi Yasushi、Kang Dongchon、Sabe Hisataka、Kinugawa Shintaro
    • Journal Title

      Cell Communication and Signaling

      Volume: 17 Issue: 1 Pages: 128-128

    • DOI

      10.1186/s12964-019-0445-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced Echo Intensity of Skeletal Muscle Is Associated With Exercise Intolerance in Patients With Heart Failure2019

    • Author(s)
      Nakano Ippei、Hori Hiroaki、Fukushima Arata、Yokota Takashi、Kinugawa Shintaro、Takada Shingo、Yamanashi Katsuma、Obata Yoshikuni、Kitaura Yasuyuki、Kakutani Naoya、Abe Takahiro、Anzai Toshihisa
    • Journal Title

      Journal of Cardiac Failure

      Volume: - Issue: 8 Pages: 30416-30419

    • DOI

      10.1016/j.cardfail.2019.09.001

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain-Derived Neurotrophic Factor Improves Limited Exercise Capacity in Mice With Heart Failure2018

    • Author(s)
      Matsumoto Junichi、et al. Hatakeyama Shigetsugu、Matsumoto Masaki、Nakayama Keiichi I.、Otsuka Yutaro、Sabe Hisataka、Tsutsui Hiroyuki、Anzai Toshihisa
    • Journal Title

      Circulation

      Volume: 138 Issue: 18 Pages: 2064-2066

    • DOI

      10.1161/circulationaha.118.035212

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protein acetylation in skeletal muscle mitochondria is involved in impaired fatty acid oxidation and exercise intolerance in heart failure2018

    • Author(s)
      Tsuda Masaya、Fukushima Arata、Matsumoto Junichi、Takada Shingo、Kakutani Naoya、Nambu Hideo、Yamanashi Katsuma、Furihata Takaaki、Yokota Takashi、Okita Koichi、Kinugawa Shintaro、Anzai Toshihisa
    • Journal Title

      Journal of Cachexia, Sarcopenia and Muscle

      Volume: 9 Issue: 5 Pages: 844-859

    • DOI

      10.1002/jcsm.12322

    • NAID

      120006626588

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Treatment with brain-derived neurotrophic factor (BDNF) for skeletal muscle abnormalities in heart failure2021

    • Author(s)
      絹川真太郎
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Skeletal muscle abnormalities in heart failure2020

    • Author(s)
      Kinugawa S
    • Organizer
      Asian Pacific Society of Cardiology Japan Circulation Society
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 運動療法代替治療法の開発2020

    • Author(s)
      絹川真太郎
    • Organizer
      第39回日本臨床運動療法学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Activation of invariant natural killer T cells by alpha-galactosylceramide ameliorates doxorubicin-induced cardiotoxicity in mice.2019

    • Author(s)
      Obata Y, Ishimori N, Saito A, Kinugawa S, Nakano I, Kakutani N, Yamanashi K, Anzai T
    • Organizer
      European Society of Cardiology Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [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
      2019 Annual Research Report
    • Int'l Joint Research
  • [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
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Brain-derived neurotrophic factor improves limited exercise capacity by regulating mitochondrial faty-acid oxidation in mice with heart failure2018

    • Author(s)
      Matsumoto J, Takada S, Kinugawa S, Furihata T, Nambu H, Kakutani N, Fukushima A, Yokota T, Tsutsui H, Anzai T
    • Organizer
      第22回日本心不全学会学術集会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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