Grant: Project Grant

We face a growing global epidemic of obesity and diabetes. About 9.3% of Canadians have diabetes, for an estimated economic cost of $12.2 billion. The most common type of diabetes is type 2 diabetes, which is associated with obesity. Fat or adipose tissue is increasingly recognized as an important and dynamic organ that grows massively when we gain weight. A number of studies suggest that scarring or fibrosis increases in adipose tissue when we gain large amounts of weight, and this fibrosis could play a part in the development of type 2 diabetes. Why and how this occurs is not clear. The overall goal of this work is to identify the signaling pathways that lead to adipose tissue fibrosis and the development of diabetes when we gain weight. Yes-associated protein 1 (YAP) has recently been found to contribute to fibrosis and chronic disease in other tissues. We have found that YAP increases in fat with obesity and type 2 diabetes. We also find that inhibiting another protein, focal adhesion kinase (FAK), seems to increase levels of YAP in fat cells. Thus, our goal is to identify the role of these signaling proteins in fat and fibrosis contributing to type 2 diabetes with obesity. First, we will measure if YAP is activated with adipose tissue fibrosis, obesity and diabetes. Then, we plan to test whether knocking out YAP can prevent adipose tissue fibrosis and diabetes. Finally, we will determine whether FAK regulates levels of YAP, contributing to fibrosis and disease. Together, these studies will help us better understand fat, fibrosis and the role they play in our metabolism. These discoveries will help us develop better treatments for obesity and diabetes in the future.