Mechanisms of human skeletal muscle remodelling with exercise

骨骼肌是一种令人难以置信的可塑性组织，它具有分解旧的和/或受损的蛋白质并合成(合成)新的功能蛋白质的非凡能力。这些过程同时且持续地发生，随着运动和营养的增加而增强，并最终起到‘重塑’这一重要组织的作用。新肌肉蛋白(MPS)的合成在很大程度上决定了肌肉是否变得更大、更强壮，例如通过合成产生力量的肌原纤维(MYO)蛋白质来进行阻力运动(REX)，和/或通过合成产生能量的线粒体(MITO)蛋白质来发展更强的耐力能力(例如耐力运动(END))。 他们说，一些肌肉蛋白质的合成可以通过摄入膳食氨基酸(AA)来增强，氨基酸是蛋白质的组成部分。然而，大多数研究集中于REX后即刻的反应，而没有考虑结束和/或之后的时间点(例如，24小时)在肌肉重建过程中的影响。因此，这项研究计划将采用独特的“嘴对肌肉”的方法来研究饮食AA如何通过稳定同位素(比正常情况下更重的AA“示踪剂”)和特殊的“固有标记蛋白质”的使用，在运动后的不同时间支持人类骨骼肌的重构。这些新的蛋白质含有“示踪剂”，使我们能够测量它们的氨基酸是如何被运送到肌肉并随后被肌肉摄取的，以用于在不同类型的运动后合成新的MYO和MITO蛋白质。为了促进我们对饮食AA如何促进运动诱导的肌肉重建的理解，我们还将测量人类肌肉中特定蛋白质的存在和位置，这些蛋白质参与将AA运输到细胞内，并调节它们如何用于构建新的肌肉。 运动还会激活卫星细胞(SC)。尽管这些肌肉干细胞有助于修复受损的肌肉纤维和/或支持生长或重塑肌肉纤维，但它们的活性主要是针对REX进行研究的，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”结合SC特异性的方法来系统地评估REX和END后MPS和SC激活的变化之间的共同调节和/或潜在的协同作用。这种多学科的方法将有助于弥合传统的以MPS和SC为中心的肌肉重塑观点之间的差距。 总的来说，这项研究项目产生的信息将提供对人类肌肉可塑性的更全面的洞察，以及调节肌肉如何因应不同类型的运动而进行重塑的机制，并对营养起到支持作用。最终，这些知识将为维持和提高人类肌肉质量和质量的最有效的营养、治疗和药理学方法提供信息。

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.