Project 451021

Obesity and diabetes have reached epidemic proportions worldwide. This situation is alarming considering that these pathologies are intimately linked to the development of important health issues including insulin resistance, non-alcoholic fatty liver disease, cardiovascular diseases and cancers. Improvements in our understanding of the molecular mechanisms regulating energy and glucose homeostasis are needed for the development of new tools to treat and prevent Chronic Societal Cardiometabolic Diseases. Such a breakthrough will help to improve the quality of life millions of Canadians. Alterations in hepatic glucose metabolism is a classic feature of obesity that commonly manifest as inappropriately high hepatic glucose production contributing to hyperglycemia. As such, a better understanding of how liver metabolism is regulated in health and disease will help to develop effective strategies to prevent and treat metabolic disorders. Dysregulations of the nervous system can result in inappropriate hepatic substrate metabolism ultimately resulting in hyperglycemia, dyslipidemia, insulin resistance, and hepatic steatosis. Despite significant progress in identifying mechanisms by which the sympathetic nervous system controls the metabolic activity of the liver, the state of knowledge is surprisingly limited. In particular, little is known about how the brain communicates with organs, including the nature of the receptors involved.