Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati College of Medicine, Cincinnati, United States.
Elife. 2019 Apr 23;8:e44876. doi: 10.7554/eLife.44876.
Skeletal muscle adapts to external stimuli such as increased work. Muscle progenitors (MPs) control muscle repair due to severe damage, but the role of MP fusion and associated myonuclear accretion during exercise are unclear. While we previously demonstrated that MP fusion is required for growth using a supra-physiological model (Goh and Millay, 2017), questions remained about the need for myonuclear accrual during muscle adaptation in a physiological setting. Here, we developed an 8 week high-intensity interval training (HIIT) protocol and assessed the importance of MP fusion. In 8 month-old mice, HIIT led to progressive myonuclear accretion throughout the protocol, and functional muscle hypertrophy. Abrogation of MP fusion at the onset of HIIT resulted in exercise intolerance and fibrosis. In contrast, ablation of MP fusion 4 weeks into HIIT, preserved exercise tolerance but attenuated hypertrophy. We conclude that myonuclear accretion is required for different facets of exercise-induced adaptive responses, impacting both muscle repair and hypertrophic growth.
骨骼肌对外界刺激（如增加工作量）具有适应性。肌肉祖细胞（MPs）可在严重损伤时控制肌肉修复，但在运动过程中 MP 融合及其相关的肌核积累的作用尚不清楚。虽然我们之前已经证明，在超生理模型中，MP 融合对于生长是必需的（Goh 和 Millay，2017），但在生理环境下，肌肉适应过程中是否需要肌核积累仍存在疑问。在这里，我们开发了一个 8 周的高强度间歇训练（HIIT）方案，并评估了 MP 融合的重要性。在 8 个月大的小鼠中，HIIT 在整个方案中导致了渐进性肌核积累和功能性肌肉肥大。在 HIIT 开始时阻断 MP 融合会导致运动不耐受和纤维化。相比之下，在 HIIT 进行到 4 周时阻断 MP 融合，可保留运动耐力但减弱了肥大。我们得出结论，肌核积累对于运动引起的适应性反应的不同方面是必需的，影响肌肉修复和肥大生长。
