The orphan nuclear receptor Rev-Erbα is a peroxisome proliferator-activated receptor (PPAR) γ target gene and promotes PPAR γ-induced adipocyte differentiation
The orphan nuclear receptor Rev-Erbα is a peroxisome proliferator-activated receptor (PPAR) γ target gene and promotes PPAR γ-induced adipocyte differentiation
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DOI：
10.1074/jbc.m304664200
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发表时间：
2003-09-26
影响因子：
4.8
通讯作者：
Staels, B
中科院分区：
文献类型：
--
作者：
Fontaine, C;Dubois, G;Staels, B
REV-Erbalpha(NR1D1)是一种孤儿核受体，编码在甲状腺受体α基因的相反链上。REV-Erbalpha基因在3T3-L1细胞脂肪细胞分化过程中被诱导表达，并在大鼠脂肪组织中大量表达。过氧化物酶体增殖物激活受体γ(PPARGamma)(NR1C3)是一种控制脂肪细胞分化和胰岛素敏感性的核受体。在此，我们发现Riglitazone激活PPARγ可在体内大鼠附睾和肾周脂肪组织以及体外培养的3T3-L1脂肪细胞中诱导REV-Erbalpha的表达。此外，激活的PPARγ通过与直接重复(DR)-2反应元件REV-DR2结合来诱导REV-Erbalpha启动子活性。反应元件的5‘或3’半位点的突变完全取消了PPARGamma的结合和转录激活，证明该位点是一种新型的功能性PPARGamma反应元件。最后，Rev-Erbalpha在3T3-L1前脂肪细胞中的异位表达增强了PPARγ配体罗格列酮诱导的脂肪细胞分化。这些结果证实了Rev-Erbalpha是脂肪组织中PPARGamma的靶基因，并证明了这种核受体作为脂肪细胞分化的促进剂的作用。
Rev-Erbalpha (NR1D1) is an orphan nuclear receptor encoded on the opposite strand of the thyroid receptor alpha gene. Rev-Erbalpha mRNA is induced during adipocyte differentiation of 3T3-L1 cells, and its expression is abundant in rat adipose tissue. Peroxisome proliferator-activated receptor gamma (PPARgamma) (NR1C3) is a nuclear receptor controlling adipocyte differentiation and insulin sensitivity. Here we show that Rev-Erbalpha expression is induced by PPARgamma activation with rosiglitazone in rat epididymal and perirenal adipose tissues in vivo as well as in 3T3-L1 adipocytes in vitro. Furthermore, activated PPARgamma induces Rev-Erbalpha promoter activity by binding to the direct repeat (DR)-2 response element Rev-DR2. Mutations of the 5' or 3' half-sites of the response element totally abrogated PPARgamma binding and transcriptional activation, identifying this site as a novel type of functional PPARgamma response element. Finally, ectopic expression of Rev-Erbalpha in 3T3-L1 preadipocytes potentiated adipocyte differentiation induced by the PPARgamma ligand rosiglitazone. These results identify Rev-Erbalpha as a target gene of PPARgamma in adipose tissue and demonstrate a role for this nuclear receptor as a promoter of adipocyte differentiation.