Grant: Operating Grant - PA: Inst of Nutrition, Metabolism and Diabetes -Bridge Funding

The prevalence of obesity and type 2 diabetes, two of the most common chronic metabolic disorders, continue to rise at an alarming rate and are both reaching epidemic proportions worldwide. Affected individuals are prone to not only the serious long term complications of excess weight and elevated blood sugar, but more importantly, cardiovascular complications. Reduced blood level of high density lipoprotein cholesterol (HDL-C), sometimes called the "good" cholesterol, a well recognized risk marker for cardiovascular disease, is particularly common in subjects with obesity and diabetes. Insulin resistance present in people with obesity and diabetes is considered a major cause of low blood level of HDL-C. My lab recently reported an unexpected observation of insulin hypersensitivity in LCAT deficient mouse, a murine model of a specific genetic form of extreme low HDL seen in humans. We further observed that the insulin hypersensitivity in LCAT deficient mice confers resistance of these animals to diet induced diabetes and obesity. We propose to further study this novel metabolic link with the major aim in exploring the underlying mechanisms for the favorable metabolic effects. The finding would provide important insights for future identification of novel therapeutic targets in the prevention of Type 2 diabetes and obesity and their serious health consequences.