Mechanisms of human skeletal muscle remodelling with exercise

运动重塑人体骨骼肌的机制

• 批准号: RGPIN-2015-04251
• 负责人: Moore, Daniel
• 金额: $ 2.11万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612856
• 关键词: Mechanisms; human; skeletal; muscle; remodelling

Skeletal muscle is an incredibly plastic tissue resulting from its remarkable ability to break down old and/or damaged proteins and make (synthesize) new functional ones. These processes occur simultaneously and continuously, are enhanced in response to exercise and nutrition, and ultimately function to ‘remodel’ this important tissue. The synthesis of new muscle proteins (MPS) significantly determines whether a muscle gets bigger and stronger, such as with resistance exercise (REX) through the synthesis of force-generating myofibrillar (MYO) proteins, and/or develop a greater endurance capacity, such as with endurance exercise (END) through the synthesis of energy-producing mitochondrial (MITO) proteins.     The synthesis of some muscle proteins can be enhanced with the ingestion of dietary amino acids (AA) - the building blocks of protein. However, most research focuses on the response immediately after REX without consideration for the effects of END and/or time points later (e.g. 24h) in the muscle remodelling process. Therefore, this research program will take a unique “mouth-to-muscle” approach to studying how dietary AA can support human skeletal muscle remodelling at various times after exercise through stable isotopes (AA “tracers” that are heavier than normal) and the use of specialized “intrinsically-labelled proteins”. These novel proteins contain “tracers” that will allow us to measure how their AA are delivered to and subsequently taken up by the muscle to be used for the synthesis of new MYO and MITO proteins after different types of exercise. To advance our understanding of how dietary AA can enhance exercise-induced muscle remodelling, we will also measure the presence and location of specific proteins in human muscle that are involved in transporting AA into the cell and regulating how they are used to build new muscle.     Exercise also activates satellite cells (SC). Although these muscle stem cells help repair damaged and/or support growing or remodelling muscle fibres, their activity is primarily investigated in response to REX only and rarely co-incident with changes in MPS. Therefore, we will also utilize novel “tracers” combined with SC-specific methods to systematically assess the co-regulation and/or potential synergy between changes in MPS and SC activation after both REX and END. This mulit-discipline approach will help bridge the gap between the traditional dichotomous MPS- and SC-centric views of muscle remodelling.     Collectively, information generated from this research program will provide a more holistic insight into the plasticity of human muscle and the mechanisms that regulate how it remodels in response to different types of exercise with a supporting role for nutrition. Ultimately, this knowledge will inform the most effective nutraceutical, therapeutic, and pharmacological approaches to maintain and enhance muscle mass and quality in humans.

骨骼肌是一种令人难以置信的可塑性组织，具有分解旧的和/或受损的蛋白质并制造（合成）新的功能性蛋白质的卓越能力。这些过程同时连续发生，并因运动和营养而增强，并最终发挥“重塑”这一重要组织的作用。新肌肉蛋白 (MPS) 的合成显着决定肌肉是否变得更大更强，例如通过合成产生力的肌原纤维 (MYO) 蛋白进行抗阻运动 (REX)，和/或开发更大的耐力能力，例如通过合成产生能量的线粒体 (MITO) 蛋白进行耐力运动 (END)。     摄入膳食氨基酸 (AA)（蛋白质的组成部分）可以增强某些肌肉蛋白质的合成。然而，大多数研究都集中在 REX 后立即的反应，而不考虑 END 和/或肌肉重塑过程中稍后时间点（例如 24 小时）的影响。因此，该研究项目将采用独特的“口到肌肉”方法，研究饮食中的AA如何通过稳定同位素（比正常重的AA“示踪剂”）和专门的“内在标记蛋白”的使用，支持运动后不同时间的人体骨骼肌重塑。这些新型蛋白质含有“示踪剂”，使我们能够测量它们的 AA 如何传递到肌肉并随后被肌肉吸收，用于在不同类型的运动后合成新的 MYO 和 MITO 蛋白质。为了加深我们对膳食 AA 如何增强运动诱发的肌肉重塑的理解，我们还将测量人体肌肉中特定蛋白质的存在和位置，这些蛋白质参与将 AA 运输到细胞中并调节它们如何用于构建新肌肉。     运动还能激活卫星细胞（SC）。尽管这些肌肉干细胞有助于修复受损和/或支持肌肉纤维的生长或重塑，但它们的活性主要仅针对 REX 进行研究，很少与 MPS 的变化同时发生。因此，我们还将利用新颖的“示踪剂”与 SC 特异性方法相结合，系统地评估 REX 和 END 后 MPS 和 SC 激活变化之间的共同调节和/或潜在协同作用。这种多学科方法将有助于弥合传统的以 MPS 和 SC 为中心的肌肉重塑二元观点之间的差距。     总的来说，该研究项目产生的信息将提供对人体肌肉可塑性的更全面的了解，以及调节肌肉如何重塑以响应不同类型运动的机制，并具有营养支持作用。最终，这些知识将为维持和增强人类肌肉质量和质量的最有效的营养保健、治疗和药理学方法提供信息。