Rationale: Identifying the cause(s) of obesity is critical to controlling its rising prevalence and co-morbidities, including type 2 diabetes. Unfortunately, little longitudinal data exist on factors contributing to weight gain using direct measures of physical fitness, physiological difficulty of exercise, and free-living physical activity. With current R01- funding, 98 white and black premenopausal women have been comprehensively assessed in the obese and normal-weight states and are being reassessed annually for 4 years. Results to date suggest that weight gain is not explained by resting energy expenditure or fuel utilization, but by lower levels of fitness and activity energy expenditure (AEE). Extension of this grant will enable complete follow-up on all 98 women over 4 years. As well, cost-effective expansion of the sample size and range of subjects' physical fitness and AEE will occur by including follow-up of 187 women who are being weight-reduced with diet and exercise through a second R01 grant. Objectives: Number 1. To determine the mechanism and extent that physical fitness and free-living AEE contribute to long-term weight change. Number 2. To identify the underlying factors and extent to which intra- abdominal fat (IAF) increases across time. Number 3. To understand racial differences in fitness, weight-gain, IAF accumulation, and disease risk. Hypothesized outcomes are that greater fitness will increase physiological ease of exercise, resulting in a spontaneous increase in non-exercise activity thermogenesis (NEAT), free-living AEE, and weight control. Further, IAF will increase disproportionately to total fat across time, even in these pre- and peri-menopausal women. Finally, black women will have greater weight gain but lower metabolic risk, in part, due to lesser gains in IAF. Design: 285 post- obese and never-obese white and black premenopausal women, who will have been studied in the normal-weight state under current NIH funding, will undergo reassessment annually for up to 4 years. Testing on a clinical research center will include body composition (4-compartment model), IAF (CT), insulin sensitivity (FSIGT), physical fitness (muscle metabolic function using 31P MRS, VO2max, muscle strength), NEAT, and free-living AEE (doubly labeled water). Significance: Longitudinal assessments of this biracial population of premenopausal women will afford an unusual and cost-effective opportunity to gain insight into factors and mechanisms underlying long-term weight gain and increases in health risk.
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