This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000036-47
Application #
7603352
Study Section
Special Emphasis Panel (ZRR1-CR-4 (02))
Project Start
2007-04-01
Project End
2007-09-16
Budget Start
2007-04-01
Budget End
2007-09-16
Support Year
47
Fiscal Year
2007
Total Cost
$12,064
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Kelsey, Megan M; Braffett, Barbara H; Geffner, Mitchell E et al. (2018) Menstrual Dysfunction in Girls From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study. J Clin Endocrinol Metab 103:2309-2318
Kleinberger, Jeffrey W; Copeland, Kenneth C; Gandica, Rachelle G et al. (2018) Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genet Med 20:583-590
Berkowitz, Robert I; Marcus, Marsha D; Anderson, Barbara J et al. (2018) Adherence to a lifestyle program for youth with type 2 diabetes and its association with treatment outcome in the TODAY clinical trial. Pediatr Diabetes 19:191-198
Arslanian, Silva; El Ghormli, Laure; Kim, Joon Young et al. (2018) The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in ?-Cell Function in TODAY. Diabetes Care :
Kriska, Andrea; El Ghormli, Laure; Copeland, Kenneth C et al. (2018) Impact of lifestyle behavior change on glycemic control in youth with type 2 diabetes. Pediatr Diabetes 19:36-44
Venditti, E M; Tan, K; Chang, N et al. (2018) Barriers and strategies for oral medication adherence among children and adolescents with Type 2 diabetes. Diabetes Res Clin Pract 139:24-31
Gidding, Samuel S; Bacha, Fida; Bjornstad, Petter et al. (2018) Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study. J Pediatr 192:86-92.e5
Bertozzi, Beatrice; Tosti, Valeria; Fontana, Luigi (2017) Beyond Calories: An Integrated Approach to Promote Health, Longevity, and Well-Being. Gerontology 63:13-19
Arslanian, Silva; El Ghormli, Laure; Bacha, Fida et al. (2017) Adiponectin, Insulin Sensitivity, ?-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY. Diabetes Care 40:85-93
Obermeit, Lisa C; Beltran, Jessica; Casaletto, Kaitlin B et al. (2017) Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining ""symptomatic"" versus ""asymptomatic"" HAND. J Neurovirol 23:67-78

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