Leptin Regulation of Hepatic Glucose and Lipid Metabolism

More than 60,000 Canadians are diagnosed with type 2 diabetes each year, making it one of the fastest growing diseases in Canada. About 80 per cent of people with type 2 diabetes are also obese, a deadly combination that results in many long-term complications and makes diabetes the seventh leading cause of death in Canada. It is essential, therefore, to improve our understanding of the links between diabetes and obesity. The fat cell-derived hormone leptin may be a key factor linking the two. Leptin is well known to influence body weight through its ability to depress appetite and increase energy expenditure. However, leptin also has profound direct effects on metabolism. For example, mice completely deficient in leptin or the leptin receptor are obese and also develop increased fat in the blood, increased build-up of fat in tissues, and type 2 diabetes. While it is clear that leptin can act on the brain to regulate body weight, it is less clear how leptin influences glucose and fat metabolism. This is the focus of Frank Huynh’s research; in particular, the role leptin signalling in the liver may have on glucose and fat metabolism and if dysregulation of these pathways can contribute to type 2 diabetes. A better understanding of the mechanisms of leptin action would help clarify its role in the development of diabetes and obesity, potentially pointing the way to better treatment strategies.