Obesity and diabetes are chronic diseases that negatively impact metabolism of several tissues in the body. In those conditions, skeletal muscle and heart metabolism are promptly affected often leading to skeletal muscle insulin resistance and diabetic cardiomyopathy. In contrast, both exercise and calorie restriction cause metabolic adaptations in muscle and in the heart that are protective against the insults of over nutrition and diabetes. The overall objective of our research is to understand the cellular and molecular mechanisms that participate in the development of and protection against metabolic impairments in skeletal muscle and in the heart. To achieve this goal, we combine metabolomics and genomics tools with molecular and mouse genetics interventions. Ultimately, we hope to identify novel therapeutic targets for the treatment of obesity, diabetes and cardiovascular diseases.