Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

There is a well established correlation between obesity and cardiovascular complications such as heart failure. This occurs due to changes in the structure and function of the heart, yet the precise mechanisms responsible for causing these changes remain to be determined. This project will focus on the role played by substances released from fat cells (adipokines). Upon release, these substances travel in the bloodstream and can therefore have effects in other places, including the heart. In particular, we will focus on the effects of one substance called leptin. The amount of leptin circulating in the blood increases in obese individuals. We intend to characterize the effects of leptin on the cardiac extracellular matrix, a molecular network of the heart which is essential for its structure and function. In specialized cells of the heart called fibroblasts, we have determined that leptin causes changes in proteins produced by these cells. In the research plan proposed, we intend to closely examine the mechanism underlying these leptin-induced changes in cardiac fibroblasts. Furthermore, we plan to use specialized transgenic mice to examine if any leptin-mediated effects on the extracellular matrix of the heart exists. This work is very novel since the effects of leptin on the extracellular matrix of the heart have only recently begun to be investigated, and there is currently great excitement about the potential of understanding leptin's action leading to new therapeutic approaches of obesity-related heart failure.