title: The balance between gluco- and mineralo-corticoid action critically determines inflammatory adipocyte responses.
abstract: Obesity is associated with chronic inflammation. Pro-inflammatory adipokines may promote metabolic disorders and cardiovascular morbidity. However, the key mechanisms leading to obesity-related inflammation are poorly understood. The corticosteroid metabolism in adipose tissue plays a crucial role in the pathogenesis of the metabolic syndrome. Both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) mediate corticosteroid action in adipose tissue. The significance of the interplay of these receptors in mediating an inflammatory adipokine response is virtually unexplored. In the present study, we investigated the differential roles of the GR and MR in controlling the key adipose tissue functions including inflammatory adipokine expression and adipogenesis using selective stimulation with receptor agonists, acute receptor knockdown via RNA interference and newly generated knockout adipose cell lines. Selective GR stimulation of white adipocytes with dexamethasone inhibited the expression of interleukin 6 (IL6), monocyte chemoattractant protein-1 (MCP1 or CCL2 as listed in the MGI Database), tumour necrosis factor-alpha, chemerin and leptin. By contrast, selective MR stimulation with aldosterone promoted the expression of IL6, plasminogen activator inhibitor 1, chemerin and leptin. Furthermore, in the presence of an acute GR knockdown as well as in GR knockout adipocytes, corticosterone increased the gene expression of the pro-inflammatory adipokines IL6 and MCP1. Whereas GR knockout adipocytes displayed a mildly impaired adipogenesis during early differentiation, MR knockout cells completely failed to accumulate lipids. Taken together, our data demonstrate a critical role for the balance between gluco- and mineralocorticoid action in determining adipocyte responses implicated in obesity-associated inflammation and cardiovascular complications.
authors: Department of Internal Medicine I, University of Luebeck, 23538 Luebeck, Germany.
authors: J
authors: J
authors: Hoppmann
authors: N
authors: N
authors: Perwitz
authors: B
authors: B
authors: Meier
authors: M
authors: M
authors: Fasshauer
authors: D
authors: D
authors: Hadaschik
authors: H
authors: H
authors: Lehnert
authors: J
authors: J
authors: Klein
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D054392:Adipokines / Q000378:metabolism*; D000450:Aldosterone; D000818:Animals; D000893:Anti-Inflammatory Agents; D002454:Cell Differentiation; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D003345:Corticosterone; D003907:Dexamethasone; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D054392:Adipokines; D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003907:Dexamethasone; D003345:Corticosterone