Mechanisms underlying heat stress-induced skeletal muscle adaptation in prevention of sarcopenia

• Project/Area Number: 16K16565
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Sports science
• Research Institution: Juntendo University
• Principal Investigator: Kakigi Ryo 順天堂大学, スポーツ健康科学部, 非常勤助教 (70614931)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 温熱負荷 / 骨格筋 / 筋タンパク質合成 / 細胞内シグナル伝達 / サルコペニア / 熱ストレス / ラパマイシン / C2C12 / タンパク質合成 / 分化・融合 / ロイシン / タンパク質分解 / 筋肥大 / 筋萎縮 / タンパク質合成・分解

Outline of Final Research Achievements

The purpose of this study was to determine the mechanisms underlying heat stress induced-skeletal muscle adaptation, and to determine whether heat stress prevents sarcopenia. It is well known that Akt/mTOR signaling pathway involved in protein synthesis. In this study, heat stress activates mTOR signaling without Akt activation, suggesting that another factor (i.e. intracellular amino acids) is needed to activate mTOR signaling by heat stress in skeletal muscle. In addition, our data demonstrate that the combination of heat stress and leucine supplementation protected against sarcopenia.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、温熱負荷による筋肥大において筋タンパク質合成を調節するmTORシグナル伝達経路の重要性をより強調し、温熱負荷による筋適応現象メカニズムの理解に貢献するものである。また、温熱負荷は栄養と組み合わせることによってサルコペニアを予防できる可能性を示すことができたことから、今後栄養やトレーニングとの組み合わせによってさらなる応用方法の検証が行われ、より効果的なサルコペニア予防方法の開発につながると期待できる。

Research Products

• [Journal Article] Sex-specific differences in rat soleus-muscle signaling pathway responses to a bout of horizontal and downhill running. (2019)
  • Author(s): Yoshihara T, Chang SW, Tsuzuki T, Natsume T, Kakigi R, Sugiura T, Naito H.
  • Journal Title: J Physiol Biochem. Volume: 75(4) Issue: 4 Pages: 585-595
  • DOI: 10.1007/s13105-019-00712-5
  • Peer Reviewed
• [Journal Article] Body temperature elevation during exercise is essential for activating the Akt signaling pathway in the skeletal muscle of type 2 diabetic rats (2018)
  • Author(s): Tsuzuki Takamasa、Yoshihara Toshinori、Ichinoseki-Sekine Noriko、Kakigi Ryo、Takamine Yuri、Kobayashi Hiroyuki、Naito Hisashi
  • Journal Title: PLOS ONE Volume: 13 Issue: 10 Pages: e0205456-e0205456
  • DOI: 10.1371/journal.pone.0205456
  • NAID: 120007133689
  • Peer Reviewed / Open Access
• [Journal Article] Effect of a combination of astaxanthin supplementation, heat stress, and intermittent reloading on satellite cells during disuse muscle atrophy (2018)
  • Author(s): Toshinori Yoshihara, Takao Sugiura, Nobuyuki Miyaji, Yuki Yamamoto, Tsubasa Shibaguchi, Ryo Kakigi, Hisashi Naito, Katsumasa Goto, Daijiro Ohmori, Toshitada Yoshioka
  • Journal Title: Journal of Zhejiang University SCIENCE B Volume: N/A Issue: 11 Pages: 844-852
  • DOI: 10.1631/jzus.b1800076
  • Peer Reviewed / Open Access
• [Journal Article] Heat stress-induced phosphorylation of FoxO3a signalling in rat skeletal muscle. (2016)
  • Author(s): Yoshihara T, Kobayashi H, Kakigi R, Sugiura T, Naito H.
  • Journal Title: Acta Physiol (Oxf) Volume: 218(3) Issue: 3 Pages: 178-187
  • DOI: 10.1111/apha.12735
  • Peer Reviewed
• [Presentation] Effects of heat stress treatment and leucine supplementation on age-related muscle loss in mice (2018)
  • Author(s): Kakigi R, Goto A, Yoshihara T, Tsuzuki T, Naito H
  • Organizer: Experimental Biology 2018
  • Int'l Joint Research
• [Presentation] Acute heat stress under fed state stimulates muscle protein synthesis in mouse soleus muscle (2018)
  • Author(s): Kakigi R, Yoshihara T, Goto A, Naito H
  • Organizer: 2018 ACSM conference on integrative physiology of exercise
  • Int'l Joint Research
• [Presentation] 温熱刺激はサルコペニア肥満の新規治療法となり得るか？ (2018)
  • Author(s): 後藤亜由美, 柿木亮, 吉原利典, 松本綾子, 都築孝允, 古市真也, 月岡恵惟, 内藤久士
  • Organizer: 第26回日本物理療法学会学術大会
• [Presentation] 温熱刺激とロイシン摂取の組み合わせが高齢マウスの筋量および筋機能に及ぼす影響 (2017)
  • Author(s): 柿木亮、後藤亜由美、吉原利典、都築孝允、内藤久士
  • Organizer: 第72回日本体力医学会大会
• [Presentation] Effects of a bout of downhill running on skeletal muscle function and Ca2+ handling in mouse extensor digitorum longus muscle (2017)
  • Author(s): Kakigi R, Nakamura K, Eshima H, Yoshihara T, Naito H
  • Organizer: The 3rd congress, International Academy of Sportology
  • Int'l Joint Research