Grant: Operating Grant

The incidence of obesity in Canada is increasing at a staggering rate. The number of Canadians afflicted by Type 2 Diabetes Mellitus continues to grow, and we know that increased body mass is associated with the development of this disease. The rate of heart disease and stroke, the largest cause of death and disability in Western Society, is significantly elevated in those with obesity and Type 2 Diabetes. Consequently much effort has been spent on understanding how our bodies respond to excess dietary fuel and the mechanisms involved in diet-induced obesity. The body controls fuel usage, in part, through the communication of metabolic information between organs. It is becoming apparent that this communication consists of factors secreted into the blood and neuronal connections between tissues. The main objective of this project is to explore the role of neuronal connection between the brain and liver in controlling whole-body energy usage. The vagus nerve, one of the most important nerves in the body, is a two-way highway of communication between the brain and many organs. The liver-branch of this nerve controls many aspects of food intake and energy metabolism, though exactly how remains largely unknown To investigate the role the vagus nerve plays in the development of obesity, we will surgically disrupt the action of this nerve in mice. Following surgery, mice will be fed a high-fat diet for 10 weeks which normally causes weight gain and impairs insulin action. Our subsequent experiments will allow us to elucidate the role of the brain-liver axis in the development of obesity. We believe that by understanding the mechanism by which these neuronal signals alter weight gain, hormone action and fuel partitioning we will discover new targets for the prevention/treatment of obesity, diabetes and heart disease.