The glucocorticoid receptor, not the mineralocorticoid receptor, plays the dominant role in adipogenesis and adipokine production in human adipocytes

BACKGROUND: Both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) are expressed in adipose tissue and assumed to mediate cortisol actions on adipose tissue. The relative significance of the two receptors in mediating glucocorticoid regulation of adipogenesis and adipokine expression in human adipocytes has not been addressed. METHODS: We investigated the differential roles of the GR and MR in mediating glucocorticoid actions on adipogenesis and adipokine production using RNA interference in primary cultures of human preadipocytes and adipocytes. RESULTS: Both types of receptors are expressed, but levels of GR were several hundred fold higher than MR in both human preadipocytes and adipocytes. As expected, cortisol added during adipogenesis increased the differentiation of human preadipocytes. Silencing of GR, but not MR, blocked these proadipogenic actions of cortisol. In differentiated human adipocytes, addition of cortisol increased leptin and adiponectin, while suppressing interleukin-6 (IL-6), messenger RNA levels and protein secretion. Knockdown of GR by 65% decreased leptin and adiponectin while increasing IL-6 production. In addition, GR silencing blocked the effects of cortisol on adipokine expression. In contrast, although MR knockdown increased leptin, it did not affect adiponectin and IL-6 expression. CONCLUSION: Our data demonstrate that although both GR and MR have roles in regulating leptin expression, GR plays more important roles in mediating the actions of cortisol to regulate adipogenesis and adipokine production in human adipocytes.