Studies on the exercise-evoked intramuscular microenvironments and immuno-metabolism regulation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H04118
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Tohoku University
• Principal Investigator: Kanzaki Makoto 東北大学, 医工学研究科, 教授 (10272262)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 運動 / 骨格筋 / マイオカイン / 運動免疫 / 糖代謝 / ＧＬＵＴ４

Outline of Final Research Achievements

Muscle contractile activity stimulates intramuscular neutrophil recruitment establishing the microenvironment (exercise-niche) essential for muscular performance. In this research project, we revealed the physiological significance of both CX3CR1- and CXCR2-mediated signals for achieving neutrophil recruitment, upregulation of myokines, enhanced GLUT4 translocation, and adequate endurance capability. Mechanistically, a combination of CX3CR1 and CXCR2 antagonists inhibits exercise-inducible ICAM-1 and fractalkine upregulations around the endothelium and muscle-derived CXCL1 upregulation, both of which contribute to the intramuscular neutrophil accumulation in working muscles. Taken together, the exercise-evoked regional interplay among working myofibers, the adjacent endothelium, and recruited immune cells mediated through these local factors, plays a key role in the organization of the "exercise-niche" supporting the performance of skeletal muscles during exercise.

Free Research Field

運動生理学

Academic Significance and Societal Importance of the Research Achievements

運動免疫学の新概念として運動筋ニッチの生理的重要性を確認した。この運動筋ニッチは、運動依存性に惹起される異種多細胞間での相互的機能連携の場であり、その都度異なる運動強度・様式にも最適な生物応答を導き出すための統合システム制御の基点として重要な役割を担っている。本研究では急性期の運動応答性に焦点をあてたが、短期・中長期さらには加齢といった時間軸に沿った運動筋ニッチの変容は筋可塑性の作動原理となる。健全な運動効果発現のみならず、加齢や疾患に起因したそのシステム不全は筋機能、ひいては身体運動機能の弱体化を招く。運動筋ニッチ概念に基づく包括的な筋運動研究は超高齢化社会にある現代社会の吃緊の課題である。