Regulatory mechanisms of skeletal muscle responses to exercise in humans

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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.