Active endurance athletes have higher HDL-cholesterol concentrations than sedentary individuals. It is not known whether such elevations are produced by enhanced HDL synthesis, decreased catabolism, or both. Furthermore, the metabolic mechanisms by which changes in exercise or diet alter HDL concentrations are not well defined. The present proposal will compare HDL metabolism in active and sedentary men under controlled dietary conditions. We will also examine HDL metabolism in initially sedentary men undergoing exercise training and in sedentary subjects provided diets with varying contents of polyunsaturated and saturated fats. The interaction of diet and exercise will be examined in acute exercise studies and in studies providing distance runners diets high in carbohydrate or fat during periods of training and inactivity. Parameters of HDL metabolism including apoprotein synthetic and catabolic rates will be measured using radiolabeled HDL. HDL-cholesterol and apoprotein concentrations and the ultracentrifugal distribution of HDL lipids and lipoproteins will be quantitated as will the activity of lipoprotein lipase (LPLA) and hepatic triglyceride hydrolase in post-heparin plasma. These studies are designed to test the hypotheses that exercise and diet alter HDL concentrations via LPLA-mediated changes in HDL catabolism. Individual protocols address additional questions including: Do initial HDL cholesterol levels determine the change in HDL with exercise training?; Do the metabolic responses to exercise differ in men who do or do not reduce body weight?; What is the acute effect of exercise on LPLA?; Does exercise training limit the reduction in HDL produced by carbohydrate-rich diets?; By what mechanism does an increase in polyunsaturated fat reduce HDL concentrations? This research should provide insight into the regulation of HDL concentrations and the metabolic alterations produced by exercise and diet. Because of the inverse association between HDL and coronary artery disease (CAD) risk, the results should also yield information relevant to strategies for CAD prevention.
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