Grant: Travel Awards - Institute Community Support

Obesity and diabetes are growing global epidemics but we do not clearly understand why excess weight, namely obesity, is linked to problems with blood sugars known as type 2 diabetes. The growth of fat tissue and death of fat cells are thought to be important steps in the development of type 2 diabetes, but the cell signaling pathways that regulate these processes are not clear. Focal adhesion kinase (FAK) is a protein that helps transmit signals in cells. FAK is usually studied in cancers because it promotes growth, but it has not been studied well in fat, which can also grow massively. The aim of this study is to define the role of FAK in fat cells and the development of diabetes with obesity. We generated a new mouse that has the FAK gene knocked out only in fat. These mice were studied on a standard chow diet as well as in the setting of obesity from a high fat diet. Experiments were also performed using 3T3-L1 fat cells. When compared to normal siblings, knockout mice have higher blood sugars similar to diabetes. These knockout mice also have more fat tissue when they are on a normal diet, but when they eat a diet high in fat and become obese, they actually have problems with fat tissue growth. These findings were associated with increased levels of cell death and cell death signaling in the fat tissue of knockout mice or in 3T3-L1 fat cells with FAK knocked out. Preventing fat cell death by knocking down caspase 3, a protein involved in cell death, restored fat tissue growth and blood sugar levels in the knockout mice. These findings suggest that FAK is important for fat cell survival and maintaining normal blood sugars with obesity. This work improves our understanding of diabetes and obesity, and identifies future targets for therapy.