Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding
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 pathop...
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doaj-9e6c22c2d7f24cdd9c6ff3d4c17fddc42020-11-24T21:32:20ZengElsevierMolecular Metabolism2212-87782017-10-016101150116010.1016/j.molmet.2017.06.013Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feedingYachen Shen0Hyun Cheol Roh1Manju Kumari2Evan D. Rosen3Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USADivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USADivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USADivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USAObjective: 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.http://www.sciencedirect.com/science/article/pii/S2212877817304167Glucocorticoid receptorAdipose tissueInsulin resistanceLipolysisDexamethasone |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yachen Shen Hyun Cheol Roh Manju Kumari Evan D. Rosen |
spellingShingle |
Yachen Shen Hyun Cheol Roh Manju Kumari Evan D. Rosen Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding Molecular Metabolism Glucocorticoid receptor Adipose tissue Insulin resistance Lipolysis Dexamethasone |
author_facet |
Yachen Shen Hyun Cheol Roh Manju Kumari Evan D. Rosen |
author_sort |
Yachen Shen |
title |
Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding |
title_short |
Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding |
title_full |
Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding |
title_fullStr |
Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding |
title_full_unstemmed |
Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding |
title_sort |
adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding |
publisher |
Elsevier |
series |
Molecular Metabolism |
issn |
2212-8778 |
publishDate |
2017-10-01 |
description |
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. |
topic |
Glucocorticoid receptor Adipose tissue Insulin resistance Lipolysis Dexamethasone |
url |
http://www.sciencedirect.com/science/article/pii/S2212877817304167 |
work_keys_str_mv |
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