The lipid droplet-associated protein adipophilin is expressed in human trophoblasts and is regulated by peroxisomal proliferator-activated receptor-γ/retinoid X receptor
The lipid droplet-associated protein adipophilin is expressed in human trophoblasts and is regulated by peroxisomal proliferator-activated receptor-γ/retinoid X receptor
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DOI：
10.1210/jc.2003-030628
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发表时间：
2003-12-01
影响因子：
5.8
通讯作者：
Sadovsky, Y
中科院分区：
文献类型：
--
作者：
Bildirici, I;Roh, CR;Sadovsky, Y
脂肪酸的摄取和经胎盘转移对于胎儿发育至关重要。人脂肪亲和素及其鼠类直系同源脂肪细胞分化相关蛋白是脂滴相关蛋白，与脂肪细胞中的细胞脂肪酸摄取有关。核受体过氧化物酶体增殖物激活受体-γ (PPARγ) 刺激脂肪细胞对脂质的摄取，并增强胎盘滋养层细胞的分化。因此，我们假设亲脂蛋白在人类滋养层细胞中表达，并且其表达受 PPARgamma 调节。我们最初确定，亲脂蛋白在人绒毛滋养层细胞中表达，并且在培养的初代人滋养层细胞的分化过程中，亲脂蛋白表达增强。我们还发现，将培养的人滋养层细胞暴露于 PPARγ 配体曲格列酮会导致亲脂蛋白表达呈浓度依赖性增加。我们观察到 LG268 也有类似的增加，LG268 是类视黄醇 X 受体 (RXR) 的配体，是 PPARgamma 的异二聚体伴侣。最后，我们证明配体激活的 PPARgamma 和 RXR 刺激 CV-1 细胞和胎盘 JEG3 细胞系中脂肪亲和素启动子的转录活性。我们得出的结论是，在滋养层分化过程中，adipophilin 的表达增强，并被配体激活的 PPARgamma/RXR 上调。增强的脂肪亲和蛋白表达可能有助于胎盘对脂肪酸的吸收。
Uptake and transplacental transfer of fatty acids is essential for fetal development. Human adipophilin and its murine ortholog adipocyte differentiation-related protein are lipid droplet-associated proteins that are implicated in cellular fatty acid uptake in adipocytes. The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) stimulates lipid uptake by adipocytes and enhances differentiation of placental trophoblasts. We therefore hypothesized that adipophilin is expressed in human trophoblasts and that its expression is regulated by PPARgamma. We initially determined that adipophilin is expressed in human villous trophoblasts and that adipophilin expression is enhanced during differentiation of cultured primary term human trophoblasts. We also found that exposure of cultured human trophoblasts to the PPARgamma ligand troglitazone resulted in a concentration-dependent increase in adipophilin expression. We observed a similar increase with LG268, a ligand for retinoid X receptor (RXR), the heterodimeric partner of PPARgamma. Lastly, we demonstrated that ligand-activated PPARgamma and RXR stimulated the transcriptional activity of adipophilin promoter in CV-1 cells and in the placental JEG3 cell line. We conclude that the expression of adipophilin is enhanced during trophoblast differentiation and is up-regulated by ligand-activated PPARgamma/ RXR. Enhanced adipophilin expression may contribute to fatty acid uptake by the placenta.