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

背景资料：长期以来，人们都知道压力会损害健康，包括我们的身体如何调节我们的饮食习惯，我们的身体活动以及我们对血糖和血脂水平的控制。肝脏产生的高血糖和高血脂水平会增加损害身体系统的风险，这些系统有助于维持我们的代谢平衡。因此，重要的是要发现和理解影响我们身体控制糖和脂质产生的机制。 目的：这项工作旨在揭示糖皮质激素的新作用，糖皮质激素是与压力相关的激素，在大脑中改变血糖和脂质水平的全身平衡以及肝脏产生的糖和脂质。 研究项目：我们将测试如何糖皮质激素，这是在体内制造和发现，是由大脑来控制肝脏糖和脂质的生产，从而在血液中的糖和脂质水平。我们还将测试这种激素的合成类似物，这种激素广泛用于临床。我们将评估在正常条件下和高热量喂养引起的营养过剩条件下糖皮质激素在大脑中的这种作用。我们假设，大脑通过激素控制的特定途径，可以调节肝脏的糖和脂质生产和输出。因此，大脑中与压力相关的激素作用或对这种作用的抑制会影响血液中的糖和脂质水平。 影响：从拟议的研究中获得的见解将揭示可以在大脑中调节血糖和血脂水平的新途径和机制。这项研究将推进我们目前对糖皮质激素如何影响代谢的理解，不仅通过其对肝脏和脂肪组织等外周组织的已知作用，而且还通过大脑中的新作用。

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.