Elsevier

Molecular Metabolism

Volume 6, Issue 10, October 2017, Pages 1150-1160
Molecular Metabolism

Original Article
Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding

https://doi.org/10.1016/j.molmet.2017.06.013Get rights and content
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open access

Highlights

  • Adipocyte glucocorticoid receptor plays a surprisingly minor role in obesity-induced insulin resistance.

  • Adipocyte glucocorticoid receptor partially mediates dexamethasone-induced insulin resistance.

  • Glucocorticoid receptor mediates dexamethasone-induced brown fat lipid accumulation.

  • Adipocyte glucocorticoid receptor is critical for lipolysis.

Abstract

Objective

The critical role of adipose tissue in energy and nutrient homeostasis is influenced by many external factors, including overnutrition, inflammation, and exogenous hormones. Prior studies have suggested that glucocorticoids (GCs) in particular are major drivers of physiological and pathophysiological changes in adipocytes. In order to determine whether these effects directly require the glucocorticoid receptor (GR) within adipocytes, we generated adipocyte-specific GR knockout (AGRKO) mice.

Methods

AGRKO and control mice were fed chow or high fat diet (HFD) for 14 weeks. Alternatively, AGRKO and control mice were injected with dexamethasone for two months. Glucose tolerance, insulin sensitivity, adiposity, lipolysis, thermogenesis, and insulin signaling were assessed.

Results

We find that obesity, insulin resistance, and dysglycemia associated with high fat feeding do not require an intact GR in the adipocyte. However, exogenous dexamethasone (Dex) promotes metabolic dysfunction in mice, and this effect is reduced in mice lacking GR in adipocytes. The ability of Dex to promote “whitening” of brown fat is also reduced in these animals. We also show that GR is required for β-adrenergic and cold stimulation-mediated lipolysis via expression of the key lipolytic enzyme ATGL.

Conclusions

Our data suggest that the GR plays a role in normal adipose physiology via effects on lipolysis and mediates at least some of the adverse effects of exogenous steroids on metabolic function. The data also indicate that intra-adipocyte GR plays less of a role than previously believed in the local and systemic pathology associated with overnutrition.

Keywords

Glucocorticoid receptor
Adipose tissue
Insulin resistance
Lipolysis
Dexamethasone

Cited by (0)

5

Contributed equally to this work.