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

背景：众所周知，压力会恶化健康，包括我们的身体如何调节我们的饮食习惯、我们的体力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脂水平会增加破坏身体系统的风险，这些系统有助于维持我们的新陈代谢平衡。因此，重要的是发现和了解影响糖和脂肪产生的机制是如何被我们的身体控制的。目的：这项工作旨在揭示糖皮质激素在大脑中的新作用，糖皮质激素是一种与应激相关的激素，它可以改变全身血糖和血脂水平的平衡，以及肝脏产生的糖和脂。研究项目：我们将测试大脑如何利用体内制造和发现的糖皮质激素来控制肝糖和脂肪的产生，从而控制血液中的糖和脂肪水平。我们还将测试这种激素的合成类似物，它在临床环境中被广泛使用。我们将评估糖皮质激素在正常情况下和在高热量喂养导致营养过剩的情况下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，可以通过肝脏调节糖和脂肪的产生和输出。因此，大脑中与压力相关的荷尔蒙作用，或这种作用的抑制，将影响血液中的糖和脂肪水平。影响：从拟议的研究中获得的见解将揭示新的途径和机制，这些途径和机制可以在大脑中发挥作用，调节血糖和血脂水平。这项研究将推进我们目前对糖皮质激素如何影响新陈代谢的理解，不仅是通过它对肝脏和脂肪组织等外围组织的已知影响，也是通过对大脑的一种新的作用。

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.