Grant: Operating Grant

A sedentary lifestyle coupled with a diet high in fat has led to the current obesity epidemic. Obesity increases the risk of developing insulin resistance and type II diabetes. Excessive fat is linked to an increased production of factors that can alter the function of many organs, including skeletal muscle. The blood vessels that supply oxygen and nutrients to each organ are important in maintaining the appropriate function. Loss of these blood vessels is thought to occur in obesity, which may contribute to an increased risk of poor health outcomes. However, the underlying causes for this are not known. This proposal aims to examine the blood vessel networks within fat and muscle, and how they are affected by a long term high fat diet. We propose that an inhibitory regulatory protein (FoxO)is increased by the high fat diet, and contributes to the blood vessel loss. To test this, we will use a mouse model in which FoxO is deleted from the cells that make up blood vessels. We will determine whether lack of FoxO protein is sufficient to reverse the negative consequences of high fat diet on the blood vessels within fat and muscle. We also will consider whether loss of this protein in the high fat fed animals can improve their metabolism. These investigations will provide knowledge of how a high fat diet leads to loss of blood vessels, and new insight into ways in which these negative outcomes may be reversed. These findings may have potential clinical implications for treatment of obesity-associated complications that are linked to diabetes.