Regulation of human skeletal muscle adaptation to exercise training

点击翻译按钮获取中文摘要

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.