This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Elevated plasma TG concentrations, which are commonly observed in obese individuals, are an important risk factor for cardiovascular disease. Diet-induced weight loss and endurance exercise cause a reduction in plasma TG, mainly VLDL-TG, concentrations. However, the mechanisms responsible for this effect are largely unknown, and much uncertainty remians regarding the individual roles of energy intake, energy expenditure, and net energy balance in controlling plasma TG concentrations. The main goal of this project is to investigate the mechanisms by which acute alterations in energy balance, induced by diet and/or endurance exercise, regulate VLDL-TG metabolism in overweight and obese men. We hypothesize that: 1) Negative energy balance lowers plasma TG concentrations, but the mechanisms differ depending on whether it is induced by dietary calorie restriction or endurance exercise. We propose that caloric restriction decreases hepatic VLDL-TG secretion, whereas endurance exercise increases VLDL-TG plasma clearance. 2) Positive energy balance induced by excess dietary energy intake increases plasma TG concentrations, because it increased hepatic VLDL-TG secretion and decreases VLDL-TG clearance from plasma. 3) Endurance exercise compensates for the unfavorable effects of excess dietary energy intake on VLDL-TG kinetics and concentration, and vice versa, supplemental dietary energy intake abolishes the beneficial effects of exercise on VLDL-TG kinetics concentration, We propose that, compared to rest with net energy balance, exercise with maintenance of energy balance will have no effect on VLDL-TG concentration, because both VLDL-TG secretion and VLDL-TG plasma clearance are increased simultaneously. Theses hypotheses will be tested by using stable isotope labeled tracer techniques in conjunction with compartmental modeling analysis and muscle and adipose tissue biopsies, in response to acute (one-day) modification of dietary energy intake / or exercise energy expenditure in 16 overweight men. The findings from the proposed studies will a) elucidate the mechanisms responsible for the hypo-triglyceridemic effect of exercise and energy restriction, b) increase our understanding of the independent roles of energy balance and exercise in regulating TG metabolism, and c) help optimize lifestyle modifications (i.e., diet and exercise) aimed at reducing plasma TG concentrations.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
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Special Emphasis Panel (ZRR1-CR-4 (02))
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Washington University
Internal Medicine/Medicine
Schools of Medicine
Saint Louis
United States
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