The farnesoid X receptor regulates adipocyte differentiation and function by promoting peroxisome proliferator-activated receptor-gamma and interfering with the Wnt/beta-catenin pathways.

Mouaadh Abdelkarim 1 Sandrine Caron 1 Christian Duhem 1 Janne Prawitt 1 Julie Dumont 1 Anthony Lucas 1 Emmanuel Bouchaert 1 Olivier Briand 1 John Brozek 2 Folkert Kuipers 3 Catherine Fievet 1 Bertrand Cariou 1 Bart Staels 1, *
* Auteur correspondant
1 EGID - Récepteurs nucléaires, maladies cardiovasculaires et diabète
2 Genfit
3 Department of Pediatrics
Abstract : The bile acid receptor farnesoid X receptor (FXR) is expressed in adipose tissue, but its function remains poorly defined. Peroxisome proliferator-activated receptor-γ (PPARγ) is a master regulator of adipocyte differentiation and function. The aim of this study was to analyze the role of FXR in adipocyte function and to assess whether it modulates PPARγ action. Therefore, we tested the responsiveness of FXR-deficient mice (FXR(-/-)) and cells to the PPARγ activator rosiglitazone. Our results show that genetically obese FXR(-/-)/ob/ob mice displayed a resistance to rosiglitazone treatment. In vitro, rosiglitazone treatment did not induce normal adipocyte differentiation and lipid droplet formation in FXR(-/-) mouse embryonic fibroblasts (MEFs) and preadipocytes. Moreover, FXR(-/-) MEFs displayed both an increased lipolysis and a decreased de novo lipogenesis, resulting in reduced intracellular triglyceride content, even upon PPARγ activation. Retroviral-mediated FXR re-expression in FXR(-/-) MEFs restored the induction of adipogenic marker genes during rosiglitazone-forced adipocyte differentiation. The expression of Wnt/β-catenin pathway and target genes was increased in FXR(-/-) adipose tissue and MEFs. Moreover, the expression of several endogenous inhibitors of this pathway was decreased early during the adipocyte differentiation of FXR(-/-) MEFs. These findings demonstrate that FXR regulates adipocyte differentiation and function by regulating two counteracting pathways of adipocyte differentiation, the PPARγ and Wnt/β-catenin pathways.
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Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (47), pp.36759-67. 〈10.1074/jbc.M110.166231〉
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Soumis le : mardi 20 septembre 2011 - 08:35:06
Dernière modification le : lundi 8 octobre 2018 - 17:44:06
Document(s) archivé(s) le : mercredi 21 décembre 2011 - 02:20:17

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Mouaadh Abdelkarim, Sandrine Caron, Christian Duhem, Janne Prawitt, Julie Dumont, et al.. The farnesoid X receptor regulates adipocyte differentiation and function by promoting peroxisome proliferator-activated receptor-gamma and interfering with the Wnt/beta-catenin pathways.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (47), pp.36759-67. 〈10.1074/jbc.M110.166231〉. 〈inserm-00523541〉

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