The metabolic response to exercise involves the rapid mobilization and oxidation of endogenous substrates (muscle glycogen and triglycerides, plasma glucose and free fatty acids). Nonetheless, there are limited data quantifying any aspect of lipid kinetics in exercise, and no studies have delineated the factors controlling the rate of lipolysis or the rate of fat oxidation. Consequently, the general goal of the proposed project is to elucidate in humans the regulation of lipolysis and fatty acid availability in exercise, and also to determine the factors limiting fat oxidation. The following specific hypotheses related to fat mobilization will be investigated: * Endurance trained athletes have an enhanced lipolytic response to exercise, regardless of body composition. * Lipolysis is stimulated in exercise by beta adrenergic activity. * Changes in glucose and/or insulin concentration are responsible for the relationship between lipolysis and fatty acid release in exercise. Thus, we propose that hyperglycemia occurring in high intensity exercise causes Ra FFA to decrease relative to Ra glycerol. * Adenosine inhibits peripheral lipolysis in high intensity exercise. Two hypotheses will be investigated regarding fatty acid oxidation in high- intensity exercise: * Fat oxidation is limited in exercise by availability. * Long chain fatty acid oxidation is limited in exercise by transport into the mitochondria via carnitine acyl transferase (CAT). Transport is proposed to be limited by the assimilation of excess acetyl CoA resulting from a high rate of metabolism of intramuscular glycogen. These hypotheses will be investigated using new stable isotope tracer methods, the control of plasma - glucose, insulin, and fatty acid concentrations, and the administration of blocking agents. These will be the first quantitative studies of factors controlling lipid metabolism in exercising men and women.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Metabolism Study Section (MET)
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University of Texas Medical Br Galveston
Other Basic Sciences
Schools of Medicine
United States
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