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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=683156
• 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，它具有分解旧的和/或受损的蛋白质并制造（合成）新的功能性蛋白质的非凡能力。这些过程同时发生，持续不断，在运动和营养的反应中得到加强，并最终起到“重塑”这一重要组织的作用。新肌肉蛋白（MPS）的合成显著决定了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）蛋白的阻力运动（雷克斯），和/或通过合成产生能量的线粒体（MITO）蛋白的耐力运动（END）来发展更大的耐力。 一些肌肉蛋白质的合成可以通过摄入膳食氨基酸（AA）-蛋白质的构建单元来增强。然而，大多数研究集中在雷克斯后立即的反应，而没有考虑肌肉重塑过程中END和/或时间点（例如24小时）的影响。因此，这项研究计划将采取独特的“嘴对肌肉”的方法来研究饮食AA如何通过稳定同位素（比正常重的AA“示踪剂”）和使用专门的“内在标记蛋白质”来支持人体骨骼肌在运动后的不同时间重塑。这些新型蛋白质含有“示踪剂”，这将使我们能够测量它们的AA如何被递送到肌肉并随后被肌肉吸收，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如何增强运动诱导的肌肉重塑的理解，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转运到细胞中并调节它们如何用于构建新肌肉。 运动还可以激活卫星细胞（SC）。虽然这些肌肉干细胞有助于修复受损和/或支持生长或重塑肌纤维，但它们的活性主要是在响应雷克斯时进行研究的，很少与MPS的变化同时发生。因此，我们还将利用新的“示踪剂”结合SC特异性方法来系统地评估雷克斯和END后MPS和SC激活变化之间的协同调节和/或潜在协同作用。这种多学科的方法将有助于弥合肌肉重塑的传统二分法MPS和SC中心观点之间的差距。**** 总的来说，从这项研究计划中产生的信息将提供一个更全面的洞察人类肌肉的可塑性和机制，调节它如何重塑响应不同类型的运动与营养的支持作用。最终，这些知识将为最有效的保健品，治疗和药理学方法提供信息，以维持和提高人类的肌肉质量和质量。