Mechanistic coupling between obesity and mitochondrial oxidative stress in diabetic cardiomyopathy

Metabolic syndrome, featured by obesity and diabetes, is an independent risk factor for cardiovascular disease, including ischemic heart disease and diabetic cardiomyopathy. The goal of this Pilot and Feasibility project is to test the hypothesis that high fatty acid supply, often seen in obese patients, stimulates fatty acid oxidation, fuels mitochondrial respiration-coupled reactive oxygen species(ROS) production and over time leads to oxidative stress and insulin resistance in the heart. Dr. Wang will use state-of-the-art confocal imaging approaches combined with specific ROS indicators, biochemical measurements, transgenic mice and obesity mouse models to systematically investigate the causal role of high fatty acid oxidation in mitochondrial-derived ROS production in the cardiac myocytes. The results of this study will provide new insights into the causal link between obesity and diabetic cardiomyopathy.