Grant: Project Grant

Background: A key feature of diabetes and obesity is an abnormal level of fats ("lipids") in the blood. High blood levels of lipids made by the liver increase the risk of damaging bodily systems that serve to maintain our metabolism. Thus, it is important to discover and understand mechanisms that affect how lipid production and balance is controlled by our bodies and work towards the goal of lowering lipid levels in the blood, to reduce the risks of health problems associated with an imbalance in metabolism. Objective: Our research aims to unveil novel actions of glucagon, in the brain, that alters whole-body balance of lipid levels. Research project: We will test how glucagon, a hormone made and found in the body, is used by the brain to control liver lipid production, and consequently lipid levels in the blood. We will assess the action of glucagon in the brain under normal conditions and in obesity (from high calorie feeding) and in diabetes. We hypothesize that the brain, by specific pathways controlled by this hormone, alters lipid production and output by the liver. Hence, glucagon action in the brain will affect blood lipid levels. We hypothesize that nutrient excess impairs glucagon's action in the brain, which contributes to an over-production of lipids by the liver. Hence, targeting this defect will help restore blood lipid levels in conditions of obesity and diabetes. Impact: Insights gained from the proposed research will reveal new pathways and mechanisms to regulate blood lipid levels. The research will advance our current understanding of how glucagon affects lipid metabolism, not just by its known effects on tissues like the liver, but also by its novel actions in the brain. These findings will reveal putative new targets, which can help lower blood lipid levels in diabetes and obesity, and thus improve the quality of life of people affected by these conditions. This also helps to reduce the collateral effects on health care and spending.