Analysis of the Mechanisms Controlling Muscle Mass and Energy Metabolism through Exercise and Immobilization

2022 Fiscal Year Final Research Report

• Project/Area Number: 20KK0198
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Kobe University
• Principal Investigator: Wataru Ogawa 神戸大学, 医学研究科, 教授 (40294219)
• Co-Investigator(Kenkyū-buntansha): 野村 和弘 神戸大学, 医学部附属病院, 特定助教 (70450236) ; 平田 悠 神戸大学, 医学部附属病院, 医員 (70846352)
• Project Period (FY): 2020-10-27 – 2023-03-31
• Keywords: 運動 / 不動化 / 骨格筋量 / サルコペニア / 肥満

Outline of Final Research Achievements

We have analyzed the molecular mechanisms of immobilization-induced muscle atrophy in mice. As a result, it became clear that muscle protein degradation mediated by KLF15 is a critical pathological step in muscle atrophy caused by immobilization. We sought factors functioning downstream of KLF15 during the onset of immobilization-induced muscle atrophy and identified IL6. In immobilization-induced muscle atrophy, we found that inflammation occurs in skeletal muscles following protein degradation via the KLF15-IL6 pathway, which further advances muscle atrophy. We also found that the chemokine CXCL10 plays a crucial role in the progression of this inflammatory phase. We have revealed that the β2-adrenergic receptor signal in skeletal muscle plays a significant role in the enhancement of energy metabolism through exercise.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究では不動化の分子機構を制御する因子としてKLF15やIL6、CXCL10などの分子を同定た。いずれの分子もその機能を抑制することで不動化による筋萎縮が抑制されることから、これらの分子は不動化性筋萎縮の有用な創薬標的分子と考えられた。IL6及びCXCL10についてはその中和抗体が筋萎縮抑制効果をもつことを見出した点は意義が深い。これらの抗体はそれぞれ、ヒトに対して臨床応用、臨床試験が行われているため、今後、創薬展開に繋がる可能性は高い。