The Farnesoid X Receptor Regulates Adipocyte Differentiation and Function by Promoting Peroxisome Proliferator-activated Receptor-γ and Interfering with the Wnt/β-Catenin Pathways

被引：76

作者：

Abdelkarim, Mouaadh ^{[2
,3
]}

Caron, Sandrine ^{[2
,3
]}

Duhem, Christian ^{[2
,3
]}

Prawitt, Janne ^{[2
,3
]}

Dumont, Julie ^{[2
,3
]}

Lucas, Anthony ^{[2
,3
]}

Bouchaert, Emmanuel ^{[2
,3
]}

Briand, Olivier ^{[2
,3
]}

Brozek, John ^{[4
]}

Kuipers, Folkert ^{[5
]}

Fievet, Catherine ^{[2
,3
]}

Cariou, Bertrand ^{[2
,3
]}

Staels, Bart ^{[1
,2
,3
]}

机构：

[1] Inst Pasteur, INSERM, UMR1011, F-59019 Lille, France

[2] Univ Lille Nord France, F-59000 Lille, France

[3] Univ Lille 2, F-59000 Lille, France

[4] Genfit, F-59120 Loos, France

[5] Univ Groningen, Univ Med Ctr Groningen, Ctr Liver Digest & Metab Dis, Pediat Lab, NL-9713 GZ Groningen, Netherlands

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2010年 / 285卷 / 47期

关键词：

NUCLEAR RECEPTOR; BILE-ACIDS; ADIPOGENESIS; BETA; EXPRESSION; LIGANDS; PROTEIN; IDENTIFICATION; FIBROBLASTS; MYC;

D O I：

10.1074/jbc.M110.166231

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The bile acid receptor farnesoid X receptor (FXR) is expressed in adipose tissue, but its function remains poorly defined. Peroxisome proliferator-activated receptor-gamma (PPAR gamma) 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 PPAR gamma action. Therefore, we tested the responsiveness of FXR-deficient mice (FXR-/-) and cells to the PPAR gamma 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 PPAR gamma 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/beta-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 PPAR gamma and Wnt/beta-catenin pathways.

引用

页码：36759 / 36767

页数：9

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