Corticosteroid Receptor-Mediated Control of Endocrine Adipocyte Function

糖皮质激素是应激系统的重要介质，从根本上影响能量代谢。包括抑郁在内的应激相关疾病与糖皮质激素稳态失调和心血管发病率增加有关。盐皮质激素(MR)和糖皮质激素受体(GR)都介导糖皮质激素的作用，并在脂肪组织中表达。与炎症和动脉粥样硬化有关的脂肪细胞衍生激素可能作为应激、能量代谢失调和心血管发病率增加之间的分子联系发挥作用。本研究旨在阐明MR和GR在调节内分泌脂肪细胞功能中的作用。来自MR和GR基因敲除小鼠的新的脂肪线将被产生。这两种受体类型对炎性激素反应的调节的贡献将在这些行中分析。此外，还将研究利用RNA干扰击倒这两种受体的急性影响。其目的是重新定义MR对脂肪组织功能的意义，并研究糖皮质激素作用失调与心血管发病率增加之间的联系机制。

Glucocorticoids are essential mediators of the stress system and impact fundamentally on energy metabolism. Stress-related disorders including depression are associated with dysregulated glucocorticoid homeostasis and increased cardiovascular morbidity. Both the mineralocorticoid (MR) and the glucocorticoid receptor (GR) mediate glucocorticoid actions and are expressed in adipose tissue. Adipocyte-derived hormones implicated in inflammation and atherosclerosis may function as a molecular link between stress, dysregulated energy metabolism, and increased cardiovascular morbidity. The current project aims at elucidating the roles of the MR and the GR in the regulation of endocrine adipocyte function. Novel adipose lines from MR- and GR-knock-out mice will be generated. The contribution of both receptor types to the regulation of an inflammatory hormone response will be analysed in these lines. In addition, the acute effects of knocking down both receptors employing RNA interference will be investigated. The aim is to newly define the significance of the MR for adipose tissue function and to investigate mechanisms linking dysregulated glucocorticoid action with increased cardiovascular morbidity.