The role of brain glucocorticoid action on hepatic glucose and lipid metabolism

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Background: Stress has long been known to deteriorate health, including how our bodies regulate our eating habits, our physical activity, and our control of blood sugar and lipid levels. High blood levels of sugar and lipids produced by the liver increase the risk of damaging bodily systems that serve to maintain our metabolic balance. Thus, it is important to discover and understand mechanisms that affect how sugar and lipid production are controlled by our bodies. Objective: This work aims to unveil novel actions of glucocorticoids, which are stress-related hormones, in the brain that alters whole-body balance of blood sugar and lipid levels and sugar and lipid production by the liver. Research project: We will test how glucocorticoids, which are made and found in the body, are used by the brain to control liver sugar and lipid production, and consequently sugar and lipid levels in the blood. We will test also a synthetic analog of this hormone, which is widely used in a clinical setting. We will assess this action of glucorticoids in the brain under normal conditions and in conditions of nutrient excess induced by high calorie feeding. We hypothesize that the brain, by specific pathways controlled by hormones, can modulate sugar and lipid production and output by the liver. Hence, stress-related hormone action, or inhibition of this action, in the brain will affect sugar and lipid levels in the blood. Impact: Insights gained from the proposed research will reveal new pathways and mechanisms that can act in the brain to regulate blood sugar and lipid levels. The research will advance our current understanding of how glucocorticoids affect metabolism, not just by its known effects on peripheral tissues like liver and fat tissue, but also via a novel action in the brain.