Grant: Project Grant

The heart "burns" fat as a source of energy to help maintain its ability to pump blood efficiently. Although the use of fat for energy is extremely important in the healthy heart, evidence in animals has suggested that drugs that can partially inhibit the use of fat can prevent injury to the heart following a heart attack. However, one potential limitation of this approach is that fats can still enter the heart cells but by reducing the heart's ability to "burn" these fats, the fats can begin to accumulate within the heart cells. Of importance, having excess fat accumulate in hearts cells has been shown to lead to poor heart function. This fat-induced heart dysfunction may become even more apparent in obese individuals where levels of fats in the blood are very high and fats are already starting to accumulate in heart cells. In this instance, the use of these drugs may be even more harmful. One very important gatekeeper of fat entry into the heart cells is a fat transporting protein called CD36. We have shown that by reducing the activity of CD36, we can decrease the amount of fat that enters into the heart cell, which in turn limits how much fat can be burned for energy yet reduces the accumulation of fat. Thus, we speculate that drugs that inhibit CD36 may be much more beneficial than existing drugs that partially inhibit the use of fat. Based on this, we will test whether inhibition of CD36 function (which will decrease fat uptake into the heart as well as limit the use of fat for energy) is beneficial or detrimental to the heart in a variety of diseased states. These studies will ultimately lead to a better understanding of the importance of CD36 in the heart as well as allow us to ascertain whether drugs designed to inhibit CD36 in the heart (or related pathways that partially inhibit the use of fat for energy) may contribute to improving the performance of the heart in patients with heart disease and/or obesity.