The overall aim of this research project is to determine the effects of weight-loss and exercise on muscle oxidative capacity and muscle endurance in obesity. The following specific aims will be tested: 1) Measure the expression of transcription factors (PGC-1, PPARalpha, and NRF-1 & 2) and their target proteins that regulate oxidative metabolism in the knee extensor muscles, and assess fatigue resistance using these muscles in healthy lean and pre-diabetic obese women. 2) Determine the effect of weight-loss on the expression of muscle transcription factors and target proteins that regulate muscle oxidative metabolism, and assess changes in whole-muscle fatigue resistance after weight loss in pre-diabetic obese women. 3) Determine the effect of adding endurance exercise training to a weight loss program on the expression of PGC-1, PPARalpha, NRF-1 & 2 in skeletal muscle, muscle fatigue resistance, and whole-body insulin sensitivity. Initially, a cross-sectional comparison will made to characterize differences in these variables in obese vs. lean subjects. The obese women will then be reevaluated following 12% weight loss (through diet only or diet plus exercise) to examine the influence of weight-loss with or without exercise on these parameters.
