Preventive effects of low-intensity exercise on cancer cachexia-induced muscle atrophy

• Project/Area Number: 16K21517
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Rehabilitation science/Welfare engineering; Applied health science
• Research Institution: Osaka Health Science University (2017-2018); Osaka Yukioka College of Health Science (2016)
• Principal Investigator: Tanaka Minoru 大阪保健医療大学, 大阪保健医療大学 保健医療学部, 講師 (00735508)
• Research Collaborator: FUJINO Hidemi ; SUGIMOTO Ken
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 癌悪液質 / 筋萎縮 / 運動 / 筋量減少 / 運動効果 / マイオカイン / 遅筋 / 速筋 / 医療・福祉 / リハビリテーション / 癌 / 悪液質

Outline of Final Research Achievements

The purpose of present study was to evaluate the effects and to clarify the mechanism of low-intensity endurance exercise on cancer cachexia-induced muscle atrophy. We analyzed the changes in muscle mass and the gene and protein expression levels of major regulators or indicators of skeletal muscle protein degradation and synthesis pathway in the soleus muscles. Low-intensity exercise inhibited the muscle mass loss through a suppression of the ubiquitin-proteasome pathway, increased hypoxia-inducible factor- 1α (HIF-1α) and phosphorylated AMP-activated protein kinase (AMPK), and inhibited the deactivation of mammalian target of rapamycin (mTOR) pathway in the soleus muscle, which contributed to the prevention of cancer cachexia-induced muscle atrophy. These results suggest that low-intensity exercise has the potential to become an effective therapeutic intervention for the prevention of cancer cachexia-induced muscle atrophy.

Academic Significance and Societal Importance of the Research Achievements

本課題の結果から，低強度全身運動は筋タンパク質合成低下を抑制させることにより，癌悪液質に伴う筋萎縮の予防に効果的であることが示唆された．低強度運動が癌悪液質に伴う筋萎縮に有効な運動強度であることおよびその筋量減少予防の機序の一部が明らとなったことで、他の治療法との併用を可能にし、悪液質に対する治療法における選択の幅が広がると考えられる。以上より、本課題の結果が、癌患者における運動療法の適応範囲拡大につながる可能性があるという点から、本課題の結果は社会的意義があると考える。

Research Products

• [Journal Article] Preventive effects of low-intensity exercise on cancer cachexia-induced muscle atrophy (2019)
  • Author(s): Tanaka M, Sugimoto K, Fujimoto T, Xie K, Takahashi T, Akasaka H, Kurinami H, Yasunobe Y, Matsumoto T, Fujino H, Rakugi H
  • Journal Title: FASEB J Volume: 27 Issue: 7 Pages: 7852-7862
  • DOI: 10.1096/fj.201802430r
  • Peer Reviewed
• [Journal Article] Overexpression of Interleukin-15 exhibits improved glucose tolerance and promotes GLUT4 translocation via AMP-Activated protein kinase pathway in skeletal muscle (2019)
  • Author(s): Fujimoto Taku、Sugimoto Ken、Takahashi Toshimasa、Yasunobe Yukiko、Xie Keyu、Tanaka Minoru、Ohnishi Yuri、Yoshida Shino、Kurinami Hitomi、Akasaka Hiroshi、Takami Yoichi、Takeya Yasushi、Yamamoto Koichi、Rakugi Hiromi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 509 Issue: 4 Pages: 994-1000
  • DOI: 10.1016/j.bbrc.2019.01.024
  • Peer Reviewed
• [Presentation] 癌悪液質に伴う筋萎縮に対する全身性運動の予防効果． (2018)
  • Author(s): 田中稔 ，藤本拓，高橋利匡，赤坂憲，杉本研
  • Organizer: 第54回日本循環器病予防学会学術大会
• [Presentation] 癌液質に伴う筋萎縮に対する低強度全身運動の萎縮予防効果． (2018)
  • Author(s): 田中稔，藤本拓，謝可宇，栗波仁美，赤坂憲，藤野英己，杉本研
  • Organizer: 第73回日本体力医学会大会
• [Presentation] 癌悪液質に伴う筋萎縮に対する低強度全身運動が筋タンパク質の合成系経路に与える効果． (2018)
  • Author(s): 田中稔，杉本研，藤本拓，謝可宇，安延由紀子，高橋利匡, 栗波仁美，赤坂憲，藤野英己，楽木宏実
  • Organizer: 第23回日本基礎理学療法学会学術大会
• [Presentation] Fiber-type specificity of cancer cachexia-induced muscle wasting is phosphorylated p70S6K-dependent (2018)
  • Author(s): Minoru Tanaka
  • Organizer: Experimental Biology 2018
  • Int'l Joint Research