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Author Spotlight: Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator
Published on: May 19, 2023
Adipocyte glucocorticoid receptor has a minor contribution in adipose tissue growth
Sébastien Desarzens1, Nourdine Faresse2
1Institute of AnatomyUniversity of Zurich, Zurich, Switzerland.
Abstract:
The glucocorticoids bind and activate both the glucocorticoid receptor (GR) as well as the mineralocorticoid receptor in adipocytes. Despite several studies to determine the function of these two receptors in mediating glucocorticoids effects, their relative contribution in adipose tissue expansion and obesity is unclear. To investigate the effect of GR in adipose tissue function, we generated an adipocyte-specific Gr-knockout mouse model (Gr(ad-ko)). These mice were submitted either to a standard diet or a high-fat high sucrose diet. We found that adipocyte-specific deletion of Gr did not affect body weight gain or adipose tissue formation and distribution. However, the lack of Gr in adipocyte promotes a diet-induced inflammation determined by higher pro-inflammatory genes expression and macrophage infiltration in the fat pads. Surprisingly, the adipose tissue inflammation in Gr(ad-ko) mice was not correlated with insulin resistance or dyslipidemia, but with disturbed glucose tolerance. Our data demonstrate that adipocyte-specific ablation of Gr in vivo may affect the adipose tissue function but not its expansion during a high calorie diet.
Insights
Deleting the glucocorticoid receptor (GR) in fat cells did not impact obesity but increased diet-induced inflammation. This inflammation was linked to impaired glucose tolerance, not insulin resistance or dyslipidemia.
Area of Science:
- Endocrinology
- Metabolic Syndrome
- Adipose Tissue Biology
Background:
- Glucocorticoids regulate metabolism via glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in adipocytes.
- The specific roles of GR and MR in adipose tissue expansion and obesity remain incompletely understood.
Purpose of the Study:
- To investigate the function of the glucocorticoid receptor (GR) in adipose tissue.
- To determine the contribution of adipocyte GR to diet-induced obesity and related metabolic changes.
Main Methods:
- Generation of an adipocyte-specific Gr-knockout mouse model (Gr(ad-ko)).
- Administration of standard and high-fat, high-sucrose diets to Gr(ad-ko) mice and controls.
- Assessment of body weight, adipose tissue mass, gene expression, macrophage infiltration, glucose tolerance, insulin resistance, and lipid profiles.
Main Results:
- Adipocyte-specific Gr deletion did not alter body weight gain or adipose tissue expansion.
- Lack of GR in adipocytes promoted diet-induced inflammation, evidenced by increased pro-inflammatory gene expression and macrophage infiltration.
- Adipose tissue inflammation in Gr(ad-ko) mice correlated with disturbed glucose tolerance but not insulin resistance or dyslipidemia.
Conclusions:
- Adipocyte GR is not essential for adipose tissue expansion during high-calorie diets.
- Adipocyte GR plays a role in modulating diet-induced adipose tissue inflammation and glucose homeostasis.
- Ablation of adipocyte GR affects adipose tissue function independently of its impact on overall expansion.
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