{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dehondt H"],"funding":["European Research Council","Agence Nationale de la Recherche","Seventh Framework Programme","European Commission","European Commission Sixth Framework Programme"],"pagination":["101686"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9958065"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["69"],"pubmed_abstract":["<h4>Objective</h4>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.<h4>Methods</h4>We first investigated the immune phenotype of epididymal WAT (eWAT) from high fat diet (HFD)-fed whole-body FXR-deficient (FXR<sup>-/-</sup>) mice by flow cytometry and gene expression analysis. We then generated adipocyte-specific FXR-deficient (Ad-FXR<sup>-/-</sup>) 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<sup>-/-</sup> mice.<h4>Results</h4>eWAT from HFD-fed whole-body FXR<sup>-/-</sup> and Ad-FXR<sup>-/-</sup> mice displayed decreased pro-inflammatory macrophage infiltration and inflammation. Ad-FXR<sup>-/-</sup> 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<sup>-/-</sup> mouse adipocytes. Finally, chromatin immunoprecipitation analysis showed that FXR binds the Gsta4 gene promoter.<h4>Conclusions</h4>These results indicate a role for the adipocyte FXR-GSTA4 axis in controlling HFD-induced inflammation and systemic glucose homeostasis."],"journal":["Molecular metabolism"],"pubmed_title":["Adipocyte-specific FXR-deficiency protects adipose tissue from oxidative stress and insulin resistance and improves glucose homeostasis."],"pmcid":["PMC9958065"],"funding_grant_id":["ANR-10-LABX-46","FP7-305707","FP6 Hepadip FP6-018734","694717"],"pubmed_authors":["Nzoussi Loubota AC","Caron S","Lefebvre P","Bongiovanni A","Chavez-Talavera O","Vallez E","Dehondt H","Lestavel S","Staels B","Haas J","Derudas B","Butruille L","Marino A","Tardivel M","Tailleux A","Dombrowicz D","Dorchies E","Kuipers F","Mogilenko DA"],"additional_accession":[]},"is_claimable":false,"name":"Adipocyte-specific FXR-deficiency protects adipose tissue from oxidative stress and insulin resistance and improves glucose homeostasis.","description":"<h4>Objective</h4>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.<h4>Methods</h4>We first investigated the immune phenotype of epididymal WAT (eWAT) from high fat diet (HFD)-fed whole-body FXR-deficient (FXR<sup>-/-</sup>) mice by flow cytometry and gene expression analysis. We then generated adipocyte-specific FXR-deficient (Ad-FXR<sup>-/-</sup>) 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<sup>-/-</sup> mice.<h4>Results</h4>eWAT from HFD-fed whole-body FXR<sup>-/-</sup> and Ad-FXR<sup>-/-</sup> mice displayed decreased pro-inflammatory macrophage infiltration and inflammation. Ad-FXR<sup>-/-</sup> 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<sup>-/-</sup> mouse adipocytes. Finally, chromatin immunoprecipitation analysis showed that FXR binds the Gsta4 gene promoter.<h4>Conclusions</h4>These results indicate a role for the adipocyte FXR-GSTA4 axis in controlling HFD-induced inflammation and systemic glucose homeostasis.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2025-05-29T22:24:17.792Z","creation":"2025-04-03T22:08:57.795Z"},"accession":"S-EPMC9958065","cross_references":{"pubmed":["36746333"],"doi":["10.1016/j.molmet.2023.101686"]}}