Examining the mechanisms for the lipolytic and antilipolytic effects of glucocorticoids in adipose tissue

检查糖皮质激素在脂肪组织中的脂肪分解和抗脂肪分解作用的机制

• 批准号: 261306-2013
• 负责人: Riddell, Michael
• 金额: $ 2.4万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630905
• 关键词: Examining; mechanisms; lipolytic; antilipolytic; effects

Glucocorticoids (GCs) are naturally produced steroid hormones released by the activation of thehypothalamo-pituitary-adrenal (HPA) axis in a circadian rhythm and during times of stress (such as with exercise or starvation). GCs such as cortisol (humans) or corticosterone (rodents) have long been thought to be critical in helping to mobilize energy substrates for the organism when energy demands may be high and perhaps when food is relatively scarce (i.e. during fasting or during prolonged exercise). It is without controversy that GCs increase blood glucose levels by increasing hepatic glucose production and by limiting glucose disposal into skeletal muscle. Most texts, journals and websites also state that GCs help mobilize free fatty acids (FFAs) from adipocytes to help provide fuel for energy metabolism during exercise and a stress response by increasing adipose tissue lipase expression and/or activity. However, we and others have recently begun to discover that GCs, in fact, rapidly lower lipolysis rates in a dose-dependent fashion in fat cells and reduce FFA mobilization, at least in the short term. The purpose of this program renewal is to determine the physiological relevance of increases in GCs during times of stress (i.e. exercise, fasting, neurogenic stress) and the underlying mechanisms by which GCs have opposing roles in adipose tissue mobilization. We hypothesize that while GCs may change the "machinery" for lipolysis by changing gene transcription of key rate limiting lipases, they are actually antilipolytic via rapid non-genomic actions. The experiments that are outlined in this proposal will provide novel and important information about how GCs alter adipose tissue metabolism during a stress response. This research continues to provide an outstanding environment for trainees in the field of physiology and metabolism who are interested in Natural Sciences.

糖皮质激素（GCs）是一种自然产生的类固醇激素，由下丘脑-垂体-肾上腺（HPA）轴在昼夜节律和压力（如运动或饥饿）时激活释放。长期以来，人们一直认为，皮质醇（人类）或皮质酮（啮齿动物）等gc在能量需求可能很高或食物相对匮乏（即禁食或长时间运动）时，对帮助生物体调动能量基质至关重要。毫无争议的是，GCs通过增加肝脏葡萄糖生成和限制葡萄糖排入骨骼肌来增加血糖水平。大多数文献、期刊和网站还指出，GCs有助于动员脂肪细胞中的游离脂肪酸（FFAs），通过增加脂肪组织脂肪酶的表达和/或活性，为运动和应激反应期间的能量代谢提供燃料。然而，我们和其他人最近开始发现，事实上，GCs在脂肪细胞中以剂量依赖的方式迅速降低脂肪分解率，并减少FFA动员，至少在短期内是这样。本程序更新的目的是确定在应激时期（即运动，禁食，神经源性应激）gc增加的生理相关性以及gc在脂肪组织动员中具有相反作用的潜在机制。我们假设，虽然GCs可能通过改变关键限速脂肪酶的基因转录来改变脂肪分解的“机制”，但它们实际上是通过快速的非基因组作用来抗脂肪分解的。本提案中概述的实验将提供关于应激反应中gc如何改变脂肪组织代谢的新颖而重要的信息。这项研究继续为生理学和代谢领域对自然科学感兴趣的学员提供了一个良好的环境。