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Role of skeletal muscle-derived IGF-I in exercise-induced enhancement of brain functions

Research Project

Project/Area Number 19K24330
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0909:Sports sciences, physical education, health sciences, and related fields
Research InstitutionKyoto University (2021-2022)
Ritsumeikan University (2019-2020)

Principal Investigator

Yokokawa Takumi  京都大学, 農学研究科, 助教 (80844323)

Project Period (FY) 2019-08-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsインスリン様成長因子1 / 骨格筋 / 脳 / 臓器連関 / 情動 / 学習 / インスリン成長因子1 / 海馬 / インスリン様成長因子1 / シナプス / インスリン様成長因子 / 運動 / IGF-I
Outline of Research at the Start

運動は、脳の健康増進効果があることが報告されているが、その分子機序は明らかでない。骨格筋のインスリン様成長因子1(IGF-I)は運動により増加する。また、血中のIGF-Iは脳に輸送され、海馬の分子応答を惹起することから、運動に伴い骨格筋から分泌されたIGF-Iが血流を介して、脳で作用する可能性があるが、IGF-Iが運動における骨格筋と脳とのインタラクションの媒介因子であることを直接的に示した研究は存在しない。本研究では、骨格筋のIGF-Iが、運動による脳の健康増進を媒介している可能性を、骨格筋特異的なIGF-I欠損マウスを用いて、行動学的、生化学的、組織学的解析により検証する。

Outline of Final Research Achievements

To clarify the contribution of adult skeletal muscle-derived insulin-like growth factor 1 (IGF-I) to brain functions, we have performed the behavioral and biochemical analysis using inducible skeletal muscle-specific IGF-I knockout (iskm-IGF-I KO) mice. In this study, we found no significant change in spontaneous locomotor activity, anxiety-like behavior, and spatial learning in iskm-IGF-I KO mice. The biochemical analysis also showed no significant effect on the expression of synaptic molecules and neural activity markers in the hippocampus of iskm-IGF-I KO mice. These results suggest the no or limited contribution of adult skeletal muscle-derived IGF-I on brain functions.

Academic Significance and Societal Importance of the Research Achievements

本研究では、これまで間接的なエビデンスにより示唆されてきた骨格筋IGF-Iの脳機能への寄与を、成熟骨格筋特異的IGF-I欠損マウスを用いて検証した。その結果、成熟骨格筋におけるIGF-Iの欠損は、自発行動量・不安様行動・学習能力に顕著な影響を及ぼさないことが明らかとなった。また、海馬の生化学解析においても、同様に顕著な影響は観察されなかった。本研究は骨格筋による脳機能制御の分子機序におけるIGF-I以外の分子の重要性を示唆するとともに、骨格筋-脳の臓器連関を検証する研究のモデルデザインとなり得る点で学術的・社会的意義を持つと考えられる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (22 results)

All 2023 2022 2021 2020 2019

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 7 results) Presentation (8 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Altered expression of synaptic proteins and adhesion molecules in the hippocampus and cortex following the onset of diabetes in nonobese diabetic mice2023

    • Author(s)
      Yokokawa Takumi、Kido Kohei、Sato Koji、Hayashi Tatsuya、Fujita Satoshi
    • Journal Title

      Physiological Reports

      Volume: 11 Issue: 8

    • DOI

      10.14814/phy2.15673

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of serum brain-derived neurotrophic factor with hepatic enzymes, AST/ALT ratio, and FIB-4 index in middle-aged and older women2022

    • Author(s)
      Yokokawa Takumi、Sasaki Shohei、Sase Kohei、Yoshii Naomi、Yasuda Jun、Hayashi Tatsuya、Fujita Satoshi
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 8 Pages: e0273056-e0273056

    • DOI

      10.1371/journal.pone.0273056

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] <scp>CRTC1</scp> deficiency, specifically in melanocortin‐4 receptor‐expressing cells, induces hyperphagia, obesity, and insulin resistance2022

    • Author(s)
      Matsumura Shigenobu、Miyakita Motoki、Miyamori Haruka、Kyo Satomi、Ishikawa Fuka、Sasaki Tsutomu、Jinno Tomoki、Tanaka Jin、Fujita Kotomi、Yokokawa Takumi、Goto Tsuyoshi、Momma Keiko、Takenaka Shigeo、Inoue Kazuo
    • Journal Title

      The FASEB Journal

      Volume: 36 Issue: 12

    • DOI

      10.1096/fj.202200617r

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of CRTC1 and CRTC2 in Sim1 cells strongly increases high-fat diet intake in female mice but has a modest impact on male mice2022

    • Author(s)
      Tanaka Jin、Ishikawa Fuka、Jinno Tomoki、Miyakita Motoki、Miyamori Haruka、Sasaki Tsutomu、Yokokawa Takumi、Goto Tsuyoshi、Inoue Kazuo、Matsumura Shigenobu
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 1 Pages: e0262577-e0262577

    • DOI

      10.1371/journal.pone.0262577

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle2022

    • Author(s)
      Egawa Tatsuro、Ogawa Takeshi、Yokokawa Takumi、Kido Kohei、Goto Katsumasa、Hayashi Tatsuya
    • Journal Title

      Journal of Applied Physiology

      Volume: 132 Issue: 2 Pages: 477-488

    • DOI

      10.1152/japplphysiol.00539.2021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between protein intake and resistance training?induced muscle hypertrophy in middle-aged women: A pilot study2022

    • Author(s)
      Yasuda Jun、Murata Kao、Hasegawa Tsubasa、Yamamura Mana、Maeo Sumiaki、Takegaki Junya、Tottori Nobuaki、Yokokawa Takumi、Mori Risako、Arimitsu Takuma、Nishikori Shu、Fujita Satoshi
    • Journal Title

      Nutrition

      Volume: 97 Pages: 111607-111607

    • DOI

      10.1016/j.nut.2022.111607

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] TLR4-Mediated Inflammatory Responses Regulate Exercise-Induced Molecular Adaptations in Mouse Skeletal Muscle2022

    • Author(s)
      Fujiyoshi Haruna、Egawa Tatsuro、Kurogi Eriko、Yokokawa Takumi、Kido Kohei、Hayashi Tatsuya
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 3 Pages: 1877-1877

    • DOI

      10.3390/ijms23031877

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stimulation of G<sub>s</sub> signaling in MC4R cells by DREADD increases energy expenditure, suppresses food intake, and increases locomotor activity in mice2022

    • Author(s)
      Matsumura Shigenobu、Miyakita Motoki、Miyamori Haruka、Kyo Satomi、Shima Daisuke、Yokokawa Takumi、Ishikawa Fuka、Sasaki Tsutomu、Jinno Tomoki、Tanaka Jin、Goto Tsuyoshi、Momma Keiko、Ishihara Kengo、Berdeaux Rebecca、Inoue Kazuo
    • Journal Title

      American Journal of Physiology-Endocrinology and Metabolism

      Volume: 322 Issue: 5 Pages: E436-E445

    • DOI

      10.1152/ajpendo.00439.2021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Caffeine increases myoglobin expression via the cyclic AMP pathway in L6 myotubes2021

    • Author(s)
      Takumi Yokokawa, Takeshi Hashimoto, Nobumasa Iwanaka
    • Journal Title

      Physiological Reports

      Volume: 9 Issue: 9 Pages: 1-1

    • DOI

      10.14814/phy2.14869

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Muscle denervation reduces mitochondrial biogenesis and mitochondrial translation factor expression in mice2020

    • Author(s)
      Yokokawa Takumi、Mori Risako、Suga Tadashi、Isaka Tadao、Hayashi Tatsuya、Fujita Satoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 527 Issue: 1 Pages: 146-152

    • DOI

      10.1016/j.bbrc.2020.04.062

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dehydroepiandrosterone activates 5′-adenosine monophosphate-activated protein kinase and suppresses lipid accumulation and adipocyte differentiation in 3T3-L1 cells2020

    • Author(s)
      Yokokawa Takumi、Sato Koji、Narusawa Ryoko、Kido Kohei、Mori Risako、Iwanaka Nobumasa、Hayashi Tatsuya、Hashimoto Takeshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 528 Issue: 3 Pages: 612-619

    • DOI

      10.1016/j.bbrc.2020.05.136

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Modified expression of vitamin D receptor and CYP27B1 in denervation-induced muscle atrophy2020

    • Author(s)
      Mori Risako、Yokokawa Takumi、Fujita Satoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 529 Issue: 3 Pages: 733-739

    • DOI

      10.1016/j.bbrc.2020.05.205

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of receptor for advanced glycation end products in microgravity-induced skeletal muscle atrophy in mice2020

    • Author(s)
      Egawa Tatsuro、Kido Kohei、Yokokawa Takumi、Fujibayashi Mami、Goto Katsumasa、Hayashi Tatsuya
    • Journal Title

      Acta Astronautica

      Volume: 176 Pages: 332-340

    • DOI

      10.1016/j.actaastro.2020.07.002

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Protective Effect of Brazilian Propolis against Glycation Stress in Mouse Skeletal Muscle2019

    • Author(s)
      Egawa T, Ohno Y, Yokoyama S, Yokokawa T, Tsuda S, Goto K, Hayashi T.
    • Journal Title

      Foods

      Volume: 8 Issue: 10 Pages: 439-439

    • DOI

      10.3390/foods8100439

    • NAID

      120006766120

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Association between Serum 25-hydroxyvitamin D concentration and muscle mass and strength in Japanese elderly people2020

    • Author(s)
      Yamamura, M., Yasuda, J., Yokokawa, T., & Fujita, S
    • Organizer
      International Conference on Frailty and Sarcopenia Research 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Time course effects of voluntary running exercise on protein products of immediate early genes in murine hippocampus2019

    • Author(s)
      Yokokawa, T., Hayashi, T., & Fujita, S.
    • Organizer
      24th Annual Congress of the European College of Sport Science
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The influence of combination of Aurantiochytrium intake and resistance exercise on AMPK and mTORC1 signaling in murine skeletal muscle2019

    • Author(s)
      Mori, R., Yokokawa, T., Katamoto, Y., Ishihara, K., Iwata, O., Asayama, Y., Suzuki, K., Fujita, S.
    • Organizer
      24th Annual Congress of the European College of Sport Science
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 骨格筋特異的IGF-I欠損が骨格筋ならびに全身性の代謝に及ぼす影響2019

    • Author(s)
      横川 拓海, 木戸康平, 森理紗子, 佐瀬晃平, 増山律子, 林達也, 藤田 聡
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 坐骨神経切除による骨格筋萎縮はビタミンD受容体およびCYP27B1のタンパク質発現量の増加を伴う2019

    • Author(s)
      森理紗子, 横川拓海, 藤田聡
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ラパマイシンは単回レジスタンス運動に伴う骨格筋のインスリン感受性亢進効果を高める2019

    • Author(s)
      木戸康平, 佐瀬晃平, 横川拓海, 藤田聡
    • Organizer
      第74回 日本体力医学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脱神経がマウス骨格筋におけるミトコンドリア翻訳因子の発現量に及ぼす影響2019

    • Author(s)
      横川拓海, 森理紗子, 菅唯志, 伊坂忠夫, 林達也, 藤田聡
    • Organizer
      第74回 日本体力医学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウスにおける経皮的電気刺激によるレジスタンス運動モデルの検討2019

    • Author(s)
      森理紗子, 横川拓海, 藤田聡
    • Organizer
      第74回 日本体力医学会大会
    • Related Report
      2019 Research-status Report

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Published: 2019-09-03   Modified: 2024-01-30  

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