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

Lee MJ, Fried SK - Int J Obes (Lond) (2014)

Bottom Line: Knockdown of GR by 65% decreased leptin and adiponectin while increasing IL-6 production.In contrast, although MR knockdown increased leptin, it did not affect adiponectin and IL-6 expression.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.

View Article: PubMed Central - PubMed

Affiliation: Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

ABSTRACT

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.

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Related in: MedlinePlus

GR mediated cortisol-regulation of adipokine production in differentiated human adipocytesGR or MR silenced human adipocytes were starved for GCs overnight and treated with 200 nM cortisol for 24h. (A) Leptin mRNA. (B) Leptin secretion. (C) Adiponectin mRNA. (D) Adiponection secretion. (E) IL-6 mRNA. (F) IL-6 secretion. Interaction GR or MR siRNA and cortisol by 2 way-ANOVA, p<0.05, p<0.01, p<0.001 for the n=4-5. Effects of cortisol treatment vs. control: *, p<0.05, **, p<0.01 by paired T test.
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Figure 4: GR mediated cortisol-regulation of adipokine production in differentiated human adipocytesGR or MR silenced human adipocytes were starved for GCs overnight and treated with 200 nM cortisol for 24h. (A) Leptin mRNA. (B) Leptin secretion. (C) Adiponectin mRNA. (D) Adiponection secretion. (E) IL-6 mRNA. (F) IL-6 secretion. Interaction GR or MR siRNA and cortisol by 2 way-ANOVA, p<0.05, p<0.01, p<0.001 for the n=4-5. Effects of cortisol treatment vs. control: *, p<0.05, **, p<0.01 by paired T test.

Mentions: We next tested if the effects of cortisol on two major adipokines, leptin and adiponectin, as well as a proinflammatory cytokine, IL-6, were mediated through GR or MR. Cortisol (200 nM, 24h) increased leptin mRNA by 10±2.4-fold (p<0.01) and secretion by 2.2-fold (p<0.05) in human adipocytes (Fig 4A and B). Although GR knockdown tended to suppress basal leptin mRNA levels by 39±11% (p=0.08), it did not affect basal leptin secretion into the culture media. GR knockdown however, blocked the cortisol-induction of leptin mRNA expression and secretion (p<0.05). In contrast, MR knockdown increased leptin mRNA levels in both basal (by 42±12.8%, p=0.04) and cortisol induced (43±6.7%, p=0.01) conditions.


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

Lee MJ, Fried SK - Int J Obes (Lond) (2014)

GR mediated cortisol-regulation of adipokine production in differentiated human adipocytesGR or MR silenced human adipocytes were starved for GCs overnight and treated with 200 nM cortisol for 24h. (A) Leptin mRNA. (B) Leptin secretion. (C) Adiponectin mRNA. (D) Adiponection secretion. (E) IL-6 mRNA. (F) IL-6 secretion. Interaction GR or MR siRNA and cortisol by 2 way-ANOVA, p<0.05, p<0.01, p<0.001 for the n=4-5. Effects of cortisol treatment vs. control: *, p<0.05, **, p<0.01 by paired T test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321810&req=5

Figure 4: GR mediated cortisol-regulation of adipokine production in differentiated human adipocytesGR or MR silenced human adipocytes were starved for GCs overnight and treated with 200 nM cortisol for 24h. (A) Leptin mRNA. (B) Leptin secretion. (C) Adiponectin mRNA. (D) Adiponection secretion. (E) IL-6 mRNA. (F) IL-6 secretion. Interaction GR or MR siRNA and cortisol by 2 way-ANOVA, p<0.05, p<0.01, p<0.001 for the n=4-5. Effects of cortisol treatment vs. control: *, p<0.05, **, p<0.01 by paired T test.
Mentions: We next tested if the effects of cortisol on two major adipokines, leptin and adiponectin, as well as a proinflammatory cytokine, IL-6, were mediated through GR or MR. Cortisol (200 nM, 24h) increased leptin mRNA by 10±2.4-fold (p<0.01) and secretion by 2.2-fold (p<0.05) in human adipocytes (Fig 4A and B). Although GR knockdown tended to suppress basal leptin mRNA levels by 39±11% (p=0.08), it did not affect basal leptin secretion into the culture media. GR knockdown however, blocked the cortisol-induction of leptin mRNA expression and secretion (p<0.05). In contrast, MR knockdown increased leptin mRNA levels in both basal (by 42±12.8%, p=0.04) and cortisol induced (43±6.7%, p=0.01) conditions.

Bottom Line: Knockdown of GR by 65% decreased leptin and adiponectin while increasing IL-6 production.In contrast, although MR knockdown increased leptin, it did not affect adiponectin and IL-6 expression.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.

View Article: PubMed Central - PubMed

Affiliation: Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus