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

Endocrine Abstracts (2008) 16 OC6.7

The mineralocorticoid receptor induces pro-inflammatory effects in white adipocytes and is essential for adipogenesis

Julia Hoppmann1, Nina Perwitz1, Mathias Fasshauer2, Dirk Hadaschik1, Hendrik Lehnert1 & Johannes Klein1,3

1University of Lubeck, Lubeck, Germany; 2University of Leipzig, Leipzig, Germany; 3University of Heidelberg, Heidelberg, Germany.

Selective enhancement of glucocorticoid action in adipose tissue has been shown to induce characteristic features of the metabolic syndrome. Adipocyte-derived factors provide a link between altered adipose tissue mass and function and cardiovascular disease. However, key mechanisms controlling these pathophysiological alterations in adipose tissue are poorly understood. Recently, both, the glucocorticoid (GR) and the mineralocorticoid receptor (MR), have been shown to mediate glucocorticoid action in adipose tissue. We investigated the role of the mineralocorticoid receptor in controlling an inflammatory adipokine response and adipocyte differentiation. Selective GR stimulation of differentiated white adipocytes with dexamethasone dose-dependently inhibited gene expression of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) by 60 and 90%, respectively. By contrast, selective MR stimulation with aldosterone significantly induced the expression of these pro-inflammatory adipokines by 50%. Furthermore, an acute knock-down of the GR in fully differentiated white adipocytes and subsequent corticosterone exposure strongly increased the mRNA expression of IL-6 and MCP-1 by 90 and 430%, respectively. Finally, novel adipose cell lines from MR- and GR-knock-out mice were generated. Whereas, preadipocytes from GR-knock-out mice showed mildly impaired accumulation of lipid droplets as compared to the wild-type control lines, MR-knock-out preadipocytes completely failed to accumulate lipid droplets.

Taken together, our results dissect selective and opposing effects of the adipose MR and GR. The MR may play a role in inducing inflammatory adipocyte responses and appears essential in controlling adipocyte differentiation. Selective targeting of corticosteroid receptors may represent new options for the prevention and treatment of the metabolic syndrome and its cardiovascular complications.

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