Adipocyte-specific FXR-deficiency protects adipose tissue from oxidative stress and insulin resistance and improves glucose homeostasis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Molecular metabolism Année : 2023

Adipocyte-specific FXR-deficiency protects adipose tissue from oxidative stress and insulin resistance and improves glucose homeostasis

Folkert Kuipers
  • Fonction : Auteur

Résumé

Objective: Obesity is associated with metabolic dysfunction of white adipose tissue (WAT). Activated adipocytes secrete pro-inflammatory cytokines resulting in the recruitment of pro-inflammatory macrophages, which contribute to WAT insulin resistance. The bile acid (BA)-activated nuclear Farnesoid X Receptor (FXR) controls systemic glucose and lipid metabolism. Here, we studied the role of FXR in adipose tissue function. Methods: We first investigated the immune phenotype of epididymal WAT (eWAT) from high fat diet (HFD)-fed whole-body FXR-deficient (FXR À/À) mice by flow cytometry and gene expression analysis. We then generated adipocyte-specific FXR-deficient (Ad-FXR À/À) mice and analyzed systemic and eWAT metabolism and immune phenotype upon HFD feeding. Transcriptomic analysis was done on mature eWAT adipocytes from HFD-fed Ad-FXR À/À mice. Results: eWAT from HFD-fed whole-body FXR À/À and Ad-FXR À/À mice displayed decreased pro-inflammatory macrophage infiltration and inflammation. Ad-FXR À/À mice showed lower blood glucose concentrations, improved systemic glucose tolerance and WAT insulin sensitivity and oxidative stress. Transcriptomic analysis identified Gsta4, a modulator of oxidative stress in WAT, as the most upregulated gene in Ad-FXR À/À mouse adipocytes. Finally, chromatin immunoprecipitation analysis showed that FXR binds the Gsta4 gene promoter. Conclusions: These results indicate a role for the adipocyte FXR-GSTA4 axis in controlling HFD-induced inflammation and systemic glucose homeostasis.
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hal-04357660 , version 1 (21-12-2023)

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Hélène Dehondt, Arianna Marino, Laura Butruille, Denis A Mogilenko, Arielle C Nzoussi Loubota, et al.. Adipocyte-specific FXR-deficiency protects adipose tissue from oxidative stress and insulin resistance and improves glucose homeostasis. Molecular metabolism, 2023, 69, pp.101686. ⟨10.1016/j.molmet.2023.101686⟩. ⟨hal-04357660⟩
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