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Evidence that the beneficial effects of exercise are mediated by myokines secreted from skeletal muscle

Research Project

Project/Area Number 18H04086
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionTokyo Metropolitan University

Principal Investigator

FUJII Nobuharu  東京都立大学, 人間健康科学研究科, 教授 (40509296)

Co-Investigator(Kenkyū-buntansha) 出口 真次  大阪大学, 大学院基礎工学研究科, 教授 (30379713)
古市 泰郎  東京都立大学, 人間健康科学研究科, 助教 (40733035)
眞鍋 康子  東京都立大学, 人間健康科学研究科, 准教授 (60467412)
中川 嘉  富山大学, 学術研究部薬学・和漢系, 教授 (80361351)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2022: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2021: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2020: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2019: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2018: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Keywordsマイオカイン / 骨格筋 / R-spondin3 / 筋線維タイプ / PDGF / 筋力増強 / 血小板由来成長因子 / 遺伝子組み換えマウス / 筋サテライト細胞 / 分泌 / サルコペニア / 運動
Outline of Final Research Achievements

We have clarified the physiological roles of three novel myokines discovered by our research group. Myokine A is a factor that induces the expression of myosin heavy chain IIb, which has the highest fast-twitch properties, in the gastrocnemius muscle, where it is rarely present. R-spondin3, a myokine secreted from type 1 muscle fibers, acts on satellite cells, which are muscle somatic stem cells, and induces their differentiation into type 1 fibers. Platelet-derived growth factor (PDGF) was a muscle strength-enhancing factor that promotes the proliferation of satellite cells and increases the contraction tension of myotube during muscle contraction.

Academic Significance and Societal Importance of the Research Achievements

マイオカインは注目を集める一方で、研究に関しては歴史が浅く、知見の集積は十分ではない。そのような背景のなか、新規に3種類のマイオカインに関して、その生理的役割を明らかにしたことは、マイオカイン研究分野を確実に前進させたといえる。また、3つのマイオカイン全てが骨格筋の質を変容させる効果を有することから、ヒトへの応用も考えられる。筋線維タイプのような、筋の質に影響を与えるファクターは、加齢や疾病によって緩やかに変化することはあるが、基本は遺伝的に決定されており、後天的に変えることは難しいとされていた。本研究ではそれを劇的に変化させるマイオカインが発見されており、これが学術・社会的意義となる。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (29 results)

All 2023 2022 2021 2020 2019 Other

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 8 results) Presentation (14 results) (of which Invited: 11 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Stable isotope-labeled carnitine reveals its rapid transport into muscle cells and acetylation during contraction2023

    • Author(s)
      Furuichi Yasuro、Goto-Inoue Naoko、Uchida Saki、Masuda Shun、Manabe Yasuko、Fujii Nobuharu L.
    • Journal Title

      Heliyon

      Volume: 9 Issue: 4 Pages: e15281-e15281

    • DOI

      10.1016/j.heliyon.2023.e15281

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PDGF-B secreted from skeletal muscle enhances myoblast proliferation and myotube maturation via activation of the PDGFR signaling cascade2023

    • Author(s)
      Hamaguchi Hiroki、Dohi Kitora、Sakai Takaomi、Taoka Masato、Isobe Toshiaki、Matsui Tsubasa S.、Deguchi Shinji、Furuichi Yasuro、Fujii Nobuharu L.、Manabe Yasuko
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 639 Pages: 169-175

    • DOI

      10.1016/j.bbrc.2022.11.085

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of chronic muscle contraction on expression of contractile and metabolic proteins in mouse primary cultured myotubes2022

    • Author(s)
      Mita Yoshitaka、Ito Miyuki、Yamada Mio、Fujii Nobuharu L.、Manabe Yasuko、Furuichi Yasuro
    • Journal Title

      The Journal of Physical Fitness and Sports Medicine

      Volume: 11 Issue: 1 Pages: 51-56

    • DOI

      10.7600/jpfsm.11.51

    • NAID

      130008141537

    • ISSN
      2186-8123, 2186-8131
    • Year and Date
      2022-01-25
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a system evaluating the contractile force of electrically stimulated myotubes from wrinkles formed on elastic substrate2022

    • Author(s)
      Hamaguchi Hiroki、Matsui Tsubasa S.、Deguchi Shinji、Furuichi Yasuro、Fujii Nobuharu L.、Manabe Yasuko
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 13818-13818

    • DOI

      10.1038/s41598-022-17548-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] R-spondin3 is a myokine that differentiates myoblasts to type I fibres2022

    • Author(s)
      Mita Yoshitaka、Zhu Haonan、Furuichi Yasuro、Hamaguchi Hiroki、Manabe Yasuko、Fujii Nobuharu L.
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 13020-13020

    • DOI

      10.1038/s41598-022-16640-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mass spectrometry imaging reveals local metabolic changes in skeletal muscle due to chronic training.2022

    • Author(s)
      Goto-Inoue N, Morisasa M, Kimura K, Mori T, Furuichi Y, Manabe Y, Fujii NL.
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: in press Issue: 6 Pages: 730-738

    • DOI

      10.1093/bbb/zbac037

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Excess Glucose Impedes the Proliferation of Skeletal Muscle Satellite Cells Under Adherent Culture Conditions.2021

    • Author(s)
      Furuichi Y, Kawabata Y, Aoki A, Mita Y, Fujii NL, Manabe.
    • Journal Title

      Front. Cell Dev. Biol.

      Volume: 9 Pages: 640399-640399

    • DOI

      10.3389/fcell.2021.640399

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of treatment with conditioned media derived from C2C12 myotube on adipogenesis and lipolysis in 3T3-L1 adipocytes2020

    • Author(s)
      Tamura K, Goto-Inoue N, Miyata K, Furuichi Y, Fujii NL, Manabe Y.
    • Journal Title

      PLoS One

      Volume: 15 Issue: 8 Pages: e0237095-e0237095

    • DOI

      10.1371/journal.pone.0237095

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] R3hdml regulates satellite cell proliferation and differentiation2019

    • Author(s)
      Sakamoto Kenichi、Furuichi Yasuro、Yamamoto Masashi、Takahashi Megumi、Akimoto Yoshihiro、Ishikawa Takahiro、Shimizu Takahiko、Fujimoto Masanori、Takada‐Watanabe Aki、Hayashi Aiko、Mita Yoshitaka、Manabe Yasuko、Fujii Nobuharu L、Ishibashi Ryoichi、Maezawa Yoshiro、Betsholtz Christer、Yokote Koutaro、Takemoto Minoru
    • Journal Title

      EMBO reports

      Volume: 20 Issue: 11 Pages: 1-12

    • DOI

      10.15252/embr.201947957

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A new in vitro muscle contraction model and its application for analysis of mTORC1 signaling in combination with contraction and beta-hydroxy-beta-methylbutyrate administration.2019

    • Author(s)
      Sato S, Nomura M, Yamana I, Uchiyama A, Furuichi Y, Manabe Y, Fujii N
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 83 Issue: 10 Pages: 1851-1857

    • DOI

      10.1080/09168451.2019.1625261

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 骨格筋の分泌と再生機能に関するナイト・サイエンス2022

    • Author(s)
      藤井宣晴,眞鍋康子,古市泰郎.
    • Organizer
      第27回バイオメカニズム・シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 骨格筋の量・機能の低下をマイオカインで防ぐ可能性2022

    • Author(s)
      藤井宣晴
    • Organizer
      第9回サルコペニア・フレイル学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] マイオカインが決定する骨格筋機能2022

    • Author(s)
      藤井宣晴,三田佳貴,濵口裕貴,古市泰郎,眞鍋康子
    • Organizer
      第6回日本リハビリテーション医学会秋季学術集会.
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 骨格筋の機能を保つマイオカイン2022

    • Author(s)
      藤井宣晴
    • Organizer
      日本基礎老化学会第43回シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 骨格筋を多角的視点から考える」- 骨格筋培養細胞の収縮力評価法の開発とその応用-2021

    • Author(s)
      眞鍋康子, 濱口裕貴, 松井翼, 出口真次, 古市泰郎, 藤井宣晴
    • Organizer
      日本農芸化学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マイオカインの最前線2021

    • Author(s)
      眞鍋康子, 三田佳貴, 古市泰郎, 藤井宣晴
    • Organizer
      日本栄養食糧学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マイオカイン研究の歴史と現状2021

    • Author(s)
      藤井宣晴
    • Organizer
      日本運動生理学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 骨格筋の「質」を制御するマイオカイン2021

    • Author(s)
      古市泰郎, 三田佳貴, 眞鍋康子, 藤井宣晴
    • Organizer
      日本体力医学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 筋幹細胞の増殖におけるグルコースの意義2021

    • Author(s)
      古市泰郎, 川端有紀,眞鍋康子,藤井宣晴
    • Organizer
      日本筋学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マイオカインを運動療法に利用するための方策2020

    • Author(s)
      藤井宣晴
    • Organizer
      第54回糖尿病学の進歩
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] マイオカインと骨格筋分子生物学2020

    • Author(s)
      藤井宣晴, 古市泰郎, 眞鍋康子
    • Organizer
      第42回日本糖尿病学会,
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 骨格筋に発現する分子Xは肝臓の脂質制御に作用する2020

    • Author(s)
      湯、小宮祐希、市田日和、三浦進司、古市泰郎、 藤井宣晴、 眞鍋康子
    • Organizer
      第75回日本体力医学学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 遅筋線維特異的に発現するマイオカインが筋サテライト細胞に与える影響について2020

    • Author(s)
      三田佳貴、朱浩男、古市泰郎、藤井宣晴、眞鍋康子
    • Organizer
      第75回日本体力医学学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高グルコースは骨格筋幹細胞の増殖を抑制する2020

    • Author(s)
      古市泰郎、川端有紀、青木美穂、眞鍋康子、藤井宣晴
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Book] 健康寿命の鍵を握る骨格筋2022

    • Author(s)
      藤井 宣晴
    • Total Pages
      227
    • Publisher
      羊土社
    • ISBN
      9784758104005
    • Related Report
      2022 Annual Research Report
  • [Remarks] 東京都立大学 運動分子生物学研究室

    • URL

      https://www.comp.tmu.ac.jp/muscle/

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Remarks] 東京都立大学 運動分子生物学研究室

    • URL

      https://www.comp.tmu.ac.jp/muscle/

    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 骨格筋TypeI細胞への分化誘導剤2022

    • Inventor(s)
      藤井宣晴 眞鍋康子 古市泰郎
    • Industrial Property Rights Holder
      藤井宣晴 眞鍋康子 古市泰郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-060451
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report
  • [Patent(Industrial Property Rights)] 骨格筋TypeI細胞への分化誘導剤2021

    • Inventor(s)
      藤井宣晴, 眞鍋康子, 古市泰郎
    • Industrial Property Rights Holder
      藤井宣晴, 眞鍋康子, 古市泰郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-060451
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2018-04-23   Modified: 2024-12-25  

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