ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 S19.2

Corticosteroid receptors and adipocytes

Johannes Klein

University of Lübeck, Lübeck, Germany.

Adipose tissue is central to the control of energy and glucose homeostasis. Modulation of corticosteroid action in adipose tissue represents a potent mechanism to alter this homeostasis. Corticosteroid hormone action in adipocytes has long been considered to be mediated by glucocorticoid receptors (GR). We and others have recently identified the mineralocorticoid receptor (MR) as a new target to modulate adipocyte function. The generation of homo- and heterodimers of the GR and the MR is essential for mediating corticosteroid actions in tissues expressing both receptor types. Using newly generated murine GR- and MR-knock-out and knock-down adipose lines from white and brown fat depots we have recently aimed at dissecting specific roles of corticosteroid receptors for controlling key adipose functions including adipogenesis, adipokine expression profiles, insulin sensitivity, and transdifferentiation from lipid-storing white towards thermogenic brown adipocytes. Recent data from our and other groups support the hypothesis that the MR is essential for adipogenesis. An imbalance between MR and GR action, e.g. in the presence of chronic selective GR stimulation or via a GR knock-down, appears to promote the development of a large white cell phenotype or predominantly pro-inflammatory responses, respectively. A better understanding of the specific MR and GR roles may, in analogy to selective estrogen receptor modulators (SERMs), contribute to the development of new therapeutic options to prevent and treat the metabolic syndrome and its cardiovascular complications.

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