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

Obesity means too much fat tissue, and it increases the chance of developing heart disease and diabetes. Yet some obese people appear to be "metabolically" healthy, meaning they have normal blood sugar, normal blood pressure, normal cholesterol levels, etc. It is therefore important to consider not just the amount of fat tissue, but also how well the fat tissue works. For fat tissue to work and store calories well, it must be able to form new fat cells from pre-fat cells. Otherwise, exisitng fat cells become overstuffed and stressed, causing them to relase factors that raise the risk for heart disease and diabetes. HYPOTHESIS: Cells involved in inflammation, called macrophages, onterfere with pre-fat cell behaviour. OBJECTIVES: We will study the products made by macrophages. We will take these macrophage products and add them to pre-fat cells. We will identify specific molecules/products that are made by the macrophages. We also will compare macrophages from blood samples from people taken before and after eating a high-fat meal. We think a high-fat meal may irritate the macrophages, and that will bother the pre-fat cells more. The fat cell functions we will measure include 1) fat cell formation from pre-fat cells, 2) growth of pre-fat cells 3) death of pre-fat cells. SIGNIFICANCE: Our studies will tell us a lot more about how macrophages can act on pre-fat cells to disrupt their function in the obese. In the future, knowledge from our studies may help develop treatments that will return fat cells to a healthier functional state in obese patients, and therefore reduce the diabetes and heart disease risk.