Grant: Operating Grant

Obesity and diabetes are debilitating diseases reaching pandemic proportions in several parts of the world. According to Statistics Canada reports, ~25% of Canadians are obese. Approximately 1 billion of the global population is obese. About 5% of Canadians have diabetes. Several hormones are involved in regulating blood glucose levels and body weight. Defects in the production, secretion and/or action of these hormones could contribute to certain types of obesity and/or diabetes. There is a great deal of interest in using naturally occurring hormones for the treatment of diabetes and obesity. Nesfatin-1 is a recently discovered natural hormone found in humans and other animals. Our research determined that the insulin producing cells in the pancreas are an abundant source of nesfatin-1. Nesfatin-1 also stimulates insulin secretion from the pancreas. We, as well others identified that nesfatin-1 inhibits the quantity of food eaten, and promote weight loss. Together, these research results highlight the important roles played by nesfatin-1 in regulating body weight and blood glucose levels. How does nesfatin-1 elicit the above-mentioned functions? Currently, this question is poorly understood. I predict that nesfatin-1 has specific effects on target organs/tissues in regulating blood glucose levels, food intake and body weight. We will elucidate how nesfatin-1 affects the stomach, pancreas and liver, three organs critical in the regulation of feeding and metabolism. In a second approach, we will determine what will happen to the body weight and blood glucose if nesfatin-1 is not produced in the body. This will be achieved using a mouse model with a dysfunctional gene encoding nesfatin-1. Together, the studies proposed here will significantly improve our understanding on nesfatin-1, an important protein. The outcome of this research will also help us further explore nesfatin-1 as a potential target molecule for innovative therapies for diabetes and obesity.