Regulation of human skeletal muscle adaptation to exercise training

碳水化合物和脂肪等燃料分解为能量涉及一系列复杂的代谢反应。对能量供应所涉及的各种代谢途径的精确调控对细胞和有机体的完整性至关重要。我的研究计划是为了研究人类骨骼肌能量代谢的调节。我特别感兴趣的是协调这种组织重塑的机制，以响应不同类型的收缩活动。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。这种变化迫使肌肉迅速调整其能量供应速度，以维持适当的功能。我们研究人类骨骼肌的方法是让人们在不同的时间段以不同的强度锻炼，从而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受试者(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少量肌肉组织样本来研究人体的反应。这些样本被分析出各种化合物，包括酶、代谢物和其他参与调节细胞能量代谢的蛋白质。我们特别感兴趣的事实是，短时间的高强度运动或间歇训练似乎能刺激新陈代谢适应，这通常与长时间的耐力型训练有关。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。目前也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。这项拟议的工作将促进我们对骨骼肌“感觉”收缩压力的机制的理解，并将这一信息转化为提高燃料利用率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.