Start Date: May 27, 2010
End Date: Sep 30, 2014
In order to complete the objectives of this proposal, we will utilize a combination of studies in humans, rodents that examine physiologic, metabolomic, genetic, and proteomic endpoints. In Objective 1, we will perform studies in humans and rodents to determine how antioxidant (vitamin E and vitamin C) supplementation affects insulin responses to exercise and obesity. The study in humans will involve analysis of exercise adaptation and insulin responses in previously untrained individuals and if antioxidant supplementation either enhances or negates these adaptations. Rodent studies will further examine molecular mechanisms underlying these adaptations. In Objective 2, we will determine the extent to which obesity, exercise, and anti-oxidant supplementation alter redox balance in animals and specific cells and to identify specific proteins whose thiol redox status is altered in obesity, exercise, and anti-oxidant supplementation. These studies will utilize transgenic mouse models and proteomic approaches. In Objective 3, we will determine the extent to which obesity, exercise, and anti-oxidant supplementation alter mitochondrial function. These studies will utilize rat models of exercise and obesity. Whole tissue and isolated mitochondria will be studied for changes in total mitochondrial content, mitochondrial gene expression, and respiration, and mitochondrial enzyme activities.