Grant: Project Grant

The prevalence and severity of obesity and diabetes worldwide has dramatically increased in the last two decades. Both obesity and diabetes are major risk factors for the development of heart failure in our society. It has long been known that obese and diabetic individuals are at high risk for developing atherosclerosis, which results in narrowing of the blood vessels and increases the likelihood of developing heart disease. More recently, it has also been shown that obesity and diabetes can increase the size of the heart (called "cardiac hypertrophy), and compromise the ability of the heart muscle to contract properly. The exact reasons how cardiac hypertrophy occurs in obese and diabetic subjects is not known. Recent evidence has suggested that an excessive use of fatty acids by the heart as an energy source may be an important contributor to abnormal heart function. In obese and diabetic individuals blood fatty acid levels are often elevated, which can lead to accumulation of fatty acid and other lipids in the heart. These fatty acids and lipids can stimulate pathways in the heart that cause cardiac hypertrophy. This accumulation of harmful fatty acids within the heart also decreases the use of sugars by the heart, which can not only make the heart less efficient, but can also compromise heart function and contribute to heart disease. We speculate that inhibition of fatty acid use by the heart can be used as a therapeutic strategy to decrease cardiac hypertrophy and improve heart function. We will achieve these objectives by using a mouse models of obesity and heart failure. Using these mice we will examine the molecular mechanisms responsible for the increased cardiac hypertrophy. We will also determine whether altering either fatty acid metabolism or sugar use by the heart can be used as a therapeutic strategy to decrease cardiac hypertrophy and improve heart function in obesity and diabetes.