Adipocyte glucocorticoid receptor has a minor contribution in adipose tissue growth

Sébastien Desarzens1, Nourdine Faresse2

  • 1Institute of AnatomyUniversity of Zurich, Zurich, Switzerland.

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.

Related Concept Videos

Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
5.8K
Hormones of the Adrenal Glands01:31

Hormones of the Adrenal Glands

Adrenal hormones play a pivotal role in maintaining the body's electrolyte balance and orchestrating responses to stress, showcasing the intricate functions of the adrenal cortex and medulla.
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
6.4K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
8.2K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.9K
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
1.3K
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
8.3K