Corticosteroid Receptor-Mediated Control of Endocrine Adipocyte Function

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.