Regulatory mechanisms of skeletal muscle responses to exercise in humans

人类骨骼肌对运动反应的调节机制

• 批准号: RGPIN-2020-06398
• 负责人: Gibala, Martin
• 金额: $ 4.74万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757743
• 关键词: Regulatory; mechanisms; skeletal; muscle; responses

Skeletal muscle is an important tissue that plays a central role in whole-body energy metabolism. This refers to the chemical reactions that convert fuels such as sugars and fats into energy. My research proposal is designed to investigate the regulation of skeletal muscle energy metabolism in humans. Skeletal muscle is a fascinating tissue to study since it can change its metabolic rate dramatically. For example, during strenuous exercise, the rate of energy demand can increase by over 100-fold compared to rest. This change forces muscle cells to rapidly adjust the rate of energy supply in order to maintain proper function. The way in which we study skeletal muscle responses in humans is to produce distinct metabolic "challenges" by asking people to exercise at different intensities for varying periods of time. We can further investigate regulatory processes by altering fuel availability (e.g., using nutritional interventions) or by studying participants with different characteristics (e.g., trained versus untrained individuals). We investigate metabolic responses by obtaining small samples of muscle tissue using the needle biopsy technique. The samples are then analyzed to determine the content of markers that provide information on the acute response to exercise, or the remodeling process that occurs through the process of physical training. My previous research highlighted the important role of intensity in regulating exercise-induced remodeling of human skeletal muscle, particularly with respect to increasing the content of mitochondria (which play an important role in energy metabolism). It also showed that certain metabolic responses to exercise may be different between males and females. My current proposal builds on our progress in these areas. First, it will determine the effect of exercise intensity and activity pattern (intermittent or continuous) on skeletal muscle remodeling, including the influence of biological sex, with a comprehensive focus on mitochondrial responses. Second, it will determine the effect of elevating blood ketones on metabolic regulation, and the potential influence of biological sex and training state on this response. Ketone bodies are derived from fatty acids in liver, and can serve as an alternative substrate during exercise. Ingestion of a ketone supplement induces nutritional ketosis without the need for restrictive dietary practices, and thus enables the direct study of this condition on metabolism. An important aspect of my proposed research is the focus on humans, highlighting the ability of my work to address regulatory mechanisms that are of direct relevance to understanding human physiology. The results of this research will advance our understanding of the fundamental processes by which exercise training increases the capacity for aerobic energy metabolism in human skeletal muscle. It may also have practical applications in the design of exercise training programs to enhance health and performance.

骨骼肌是一种重要的组织，在全身能量代谢中起着核心作用。这是指将糖和脂肪等燃料转化为能量的化学反应。我的研究计划是为了研究人类骨骼肌能量代谢的调节。骨骼肌是一个令人着迷的研究组织，因为它可以戏剧性地改变其代谢率。例如，在剧烈运动中，能量需求率可以比休息时增加100倍以上。这种变化迫使肌肉细胞迅速调整能量供应速度，以维持适当的功能。我们研究人类骨骼肌反应的方法是，通过让人们在不同的时间段以不同的强度运动来产生不同的新陈代谢“挑战”。我们可以通过改变燃料的可获得性(例如，使用营养干预)或通过研究具有不同特征的参与者(例如，受过培训的个人和未受过培训的个人)来进一步研究监管过程。我们通过使用针刺活组织技术获取小样本肌肉组织来研究代谢反应。然后对样本进行分析，以确定标记物的含量，这些标记物提供了关于运动的急性反应或通过体育训练过程发生的重塑过程的信息。我之前的研究强调了强度在调节运动诱导的人类骨骼肌重构中的重要作用，特别是在增加线粒体含量方面(线粒体在能量代谢中发挥重要作用)。研究还表明，男性和女性对运动的某些代谢反应可能是不同的。我目前的提议建立在我们在这些领域取得的进展的基础上。首先，它将确定运动强度和活动模式(间歇性或连续性)对骨骼肌重构的影响，包括生物性别的影响，并综合关注线粒体的反应。其次，它将确定血酮升高对代谢调节的影响，以及生物性别和训练状态对这一反应的潜在影响。酮体来源于肝脏中的脂肪酸，可以作为运动时的替代底物。摄取酮补充剂可以引起营养性酮症，而不需要严格的饮食习惯，因此可以直接研究这种情况对新陈代谢的影响。我提议的研究的一个重要方面是对人类的关注，突出了我的工作解决与理解人类生理学直接相关的调节机制的能力。这项研究的结果将促进我们对运动训练提高人类骨骼肌有氧能量代谢能力的基本过程的理解。它也可能在运动训练计划的设计中有实际应用，以增强健康和表现。