Regulation of human skeletal muscle adaptation to exercise training

燃料，如碳水化合物和脂肪，作为能量的分解涉及一系列复杂的代谢反应。精确调节各种代谢途径所涉及的能量供应是至关重要的细胞和生物体的完整性。我的研究计划是研究人体骨骼肌能量代谢的调节。我特别感兴趣的是在不同类型的收缩活动下协调组织重塑的机制。骨骼肌是一种令人着迷的组织，因为它可以显著地改变其代谢率。例如，在剧烈运动期间，能量需求比休息时增加100倍以上。这种变化迫使肌肉迅速调整其能量供应速率，以维持正常的功能。我们研究人类骨骼肌的方法是通过要求人们在不同的时间内进行不同强度的运动来制造不同的代谢“挑战”。我们可以通过改变燃料可用性（例如，使用营养干预）或通过研究具有不同特征的受试者（例如，训练有素的个体与未训练的个体）来进一步研究监管过程。我们通过使用针活检技术获得肌肉组织的小样本来研究人类的反应。对样品进行各种化合物分析，包括酶、代谢物和其他参与调节细胞能量代谢的蛋白质。我们特别感兴趣的是，短时间的高强度运动或间歇训练似乎能刺激代谢适应，而这种适应通常与长期耐力型训练有关。关于调节人类对不同运动刺激的适应的分子信号，还有很多需要了解的。目前还不清楚男性和女性对间歇训练的反应是否相同。本研究的主要目的是为人类骨骼肌代谢调节的基本过程提供基本的科学信息。所提出的工作将促进我们对骨骼肌“感知”收缩应力的机制的理解，并将这一信息转化为增强燃料利用和抗疲劳能力的功能适应。

The breakdown of fuels, such as carbohydrates and fats, for energy involves a complex series of metabolic reactions. Precise regulation of the various metabolic pathways involved in energy provision is vital to the integrity of the cell and organism. My research proposal is designed to investigate the regulation of energy metabolism in human skeletal muscle. I am particularly interested in the mechanisms that coordinate remodeling of this tissue in response to varying types of contractile activity. 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 the muscle to rapidly adjust its rate of energy supply in order to maintain proper function. The way in which we study skeletal muscle 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 subjects with different characteristics (e.g., trained versus untrained individuals). We investigate the responses in humans by obtaining small samples of muscle tissue using the needle biopsy technique. The samples are analyzed for various compounds including enzymes, metabolites and other proteins that are involved in regulating cellular energy metabolism. We are particularly interested in the fact that short bursts of very intense exercise, or interval training, appears to stimulate metabolic adaptations that have been typically associated with prolonged endurance-type training. There is much to learn about the molecular signals that regulate adaptations to different exercise stimuli in humans. It is also unclear if men and women respond in the same manner to interval training. The major goal of this research is to provide basic scientific information about the fundamental process of metabolic regulation in human skeletal muscle. The proposed work will advance our understanding of the mechanisms by which skeletal muscle "senses" contractile stress and translates this message into functional adaptations that enhance fuel utilization and fatigue resistance.