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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=708137
• 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塑料组织，其出色的能力分解了旧和/或受损的蛋白质并制造（合成）新功能的蛋白质。这些过程简单而连续地发生，响应于运动和营养而增强，并最终起作用以“重塑”这种重要的组织。新肌肉蛋白（MPS）的合成显着决定了肌肉是否会变得更大和强大，例如通过合成力生成力的肌原纤维（MyO）蛋白质来进行抵抗运动（REX），并/或通过能量实力（Endurance Storame（End））通过能量生产（MITOCHORDROCOCHIRAIL（MITOCOCHIAL）进行耐力（结束）。 通过摄入饮食氨基酸（AA） - 蛋白质的组成部分，可以增强某些肌肉蛋白的合成。但是，大多数研究都集中在REX后立即进行响应，而无需考虑以后的结束和/或时间点（例如24H）在肌肉重塑过程中的影响。因此，该研究计划将采用独特的“口腔对肌肉”方法来研究饮食AA如何通过稳定的同位素（aa“示踪剂”比正常重）和使用专业化的“本质上标记的蛋白质”的稳定同位素（aa“示踪剂”）在运动后的不同时间支持人类的骨骼肌肉重塑。这些新型的蛋白质包含“示踪剂”，这些蛋白质将使我们能够测量其AA的递送方式并随后被肌肉所吸收，以用于在不同类型的运动后用于合成新的Myo和Mito蛋白。为了促进我们对饮食AA如何增强运动引起的肌肉重塑的理解，我们还将测量特定蛋白在人类肌肉中的存在和位置，这些蛋白在将AA转运到细胞中并调节如何使用新肌肉。 运动还激活卫星细胞（SC）。尽管这些肌肉干细胞有助于修复受损和/或支持生长或重塑的肌肉纤维，但主要研究其活性仅对REX响应，并且很少与MPS变化共同构成。因此，我们还将利用新颖的“示踪剂”与SC特异性方法相结合，以系统地评估REX和END后MPS和SC激活之间的变化之间的共同调节和/或潜在的协同作用。这种混乱的学科方法将有助于弥合传统的二分法MPS和以SC为中心的肌肉重塑观点之间的差距。 从该研究计划中产生的信息总的来说，将为人类肌肉的可塑性以及调节其对不同类型的运动的重塑的机制提供更全面的见解，并具有营养的支持作用。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，治疗和药物方法提供信息。