Grant: Fellowship: Priority Announcement - Refugee Training Initiative

Obesity puts people at huge risk for developing diabetes. Current research has spent a major effort on understanding how the increased sugar and fat in our diet has negative actions on the skeletal muscle that cause obesity-related diabetes. However, this approach has not resulted in any successful new drugs for this disease. We will take a different approach, and investigate how a different nutrient energy source, the ketone body, may be a critical factor responsible for obesity-related diabetes. Ketone bodies are a less common fuel source in the body. They are made in the liver during starvation, and used as an energy source by the brain, and other organs such as the heart and skeletal muscle. The situation of diabetes is commonly referred to as "starvation in the midst of plenty," to suggest that the body of a patient with diabetes thinks it is starving, even though their bodily organs are being supplied with a high amount of sugar and fats. Thus, we believe this "starvation in the midst of plenty" environment that diabetic patients live with provides a horrible situation where ketone bodies are continually being made and used for energy, even though these patients are not starving. In order to test our hypothesis, we will create genetically modified mice that have reduced metabolism of these ketone bodies only. We will test whether our genetically modified mice are protected against the development of diabetes, when fed a diet enriched in fat and sugar that causes significant obesity over time. In addition, we will use specialized techniques to increase metabolism of ketone bodies in lean and healthy mice, and test whether increasing ketone body metabolism can cause diabetes. In summary, our research may lead to the discovery of new drugs that can treat and/or prevent obesity-related diabetes.