Adipocyte Glucocorticoid Receptor Activation With High Glucocorticoid Doses Impairs Healthy Adipose Tissue Expansion by Repressing Angiogenesis - Sorbonne Université Access content directly
Journal Articles (Data Paper) Diabetes Year : 2024

Adipocyte Glucocorticoid Receptor Activation With High Glucocorticoid Doses Impairs Healthy Adipose Tissue Expansion by Repressing Angiogenesis

L'activation du récepteur adipocytaire aux glucocorticoïdes par de fortes doses de glucocorticoïdes altère l'expansion saine du tissu adipeux en réprimant l'angiogenèse

Anna Vali
  • Function : Author
Héloïse Dalle
  • Function : Author
Alya Loubaresse
  • Function : Author
Jérôme Gilleron
  • Function : Author
Emmanuelle Havis
  • Function : Author
Marie Garcia
  • Function : Author
Carine Beaupère
  • Function : Author
Clémentine Denis
  • Function : Author
Natacha Roblot
  • Function : Author
Karine Poussin
  • Function : Author
Tatiana Ledent
  • Function : Author
Benjamin Bouillet
Mireille Cormont
  • Function : Author
Jean-François Tanti
  • Function : Author
Jacqueline Capeau
  • Function : Author

Abstract

In humans, glucocorticoids (GCs) are commonly prescribed because of their anti-inflammatory and immunosuppressive properties. However, high doses of GCs often lead to side effects, including diabetes and lipodystrophy. We recently reported that adipocyte glucocorticoid receptor (GR)–deficient (AdipoGR-KO) mice under corticosterone (CORT) treatment exhibited a massive adipose tissue (AT) expansion associated with a paradoxical improvement of metabolic health compared with control mice. However, whether GR may control adipose development remains unclear. Here, we show a specific induction of hypoxia-inducible factor 1α (HIF-1α) and proangiogenic vascular endothelial growth factor A (VEGFA) expression in GR-deficient adipocytes of AdipoGR-KO mice compared with control mice, together with an increased adipose vascular network, as assessed by three-dimensional imaging. GR activation reduced HIF-1α recruitment to the Vegfa promoter resulting from Hif-1α downregulation at the transcriptional and posttranslational levels. Importantly, in CORT-treated AdipoGR-KO mice, the blockade of VEGFA by a soluble decoy receptor prevented AT expansion and the healthy metabolic phenotype. Finally, in subcutaneous AT from patients with Cushing syndrome, higher VEGFA expression was associated with a better metabolic profile. Collectively, these results highlight that adipocyte GR negatively controls AT expansion and metabolic health through the downregulation of the major angiogenic effector VEGFA and inhibition of vascular network development. Article Highlights

Dates and versions

hal-04453731 , version 1 (12-02-2024)

Identifiers

Cite

Anna Vali, Héloïse Dalle, Alya Loubaresse, Jérôme Gilleron, Emmanuelle Havis, et al.. Adipocyte Glucocorticoid Receptor Activation With High Glucocorticoid Doses Impairs Healthy Adipose Tissue Expansion by Repressing Angiogenesis. Diabetes, 2024, 73 (2), pp.211-224. ⟨10.2337/db23-0165⟩. ⟨hal-04453731⟩
5 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More