| First Author | Dehondt H | Year | 2023 |
| Journal | Mol Metab | Volume | 69 |
| Pages | 101686 | PubMed ID | 36746333 |
| Mgi Jnum | J:355417 | Mgi Id | MGI:7441411 |
| Doi | 10.1016/j.molmet.2023.101686 | Citation | Dehondt H, et al. (2023) Adipocyte-specific FXR-deficiency protects adipose tissue from oxidative stress and insulin resistance and improves glucose homeostasis. Mol Metab 69:101686 |
| abstractText | 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(-/-)) mice by flow cytometry and gene expression analysis. We then generated adipocyte-specific FXR-deficient (Ad-FXR(-/-)) 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(-/-) mice. RESULTS: eWAT from HFD-fed whole-body FXR(-/-) and Ad-FXR(-/-) mice displayed decreased pro-inflammatory macrophage infiltration and inflammation. Ad-FXR(-/-) 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(-/-) 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. |
