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Peroxisome Proliferator-Activated Receptor γ Target Gene Encoding a Novel Angiopoietin-Related Protein Associated with Adipose Differentiation

机译:过氧化物酶体增殖物激活受体γ靶基因编码与脂肪分化相关的新型血管生成素相关蛋白。

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The nuclear receptor peroxisome proliferator-activated receptor γ regulates adipose differentiation and systemic insulin signaling via ligand-dependent transcriptional activation of target genes. However, the identities of the biologically relevant target genes are largely unknown. Here we describe the isolation and characterization of a novel target gene induced by PPARγ ligands, termed PGAR (for PPARγ angiopoietin related), which encodes a novel member of the angiopoietin family of secreted proteins. The transcriptional induction of PGAR follows a rapid time course typical of immediate-early genes and occurs in the absence of protein synthesis. The expression of PGAR is predominantly localized to adipose tissues and placenta and is consistently elevated in genetic models of obesity. Hormone-dependent adipocyte differentiation coincides with a dramatic early induction of the PGAR transcript. Alterations in nutrition and leptin administration are found to modulate the PGAR expression in vivo. Taken together, these data suggest a possible role for PGAR in the regulation of systemic lipid metabolism or glucose homeostasis.
机译:核受体过氧化物酶体增殖物激活受体γ通过靶基因的配体依赖性转录激活来调节脂肪分化和全身性胰岛素信号传导。但是,生物学上相关的靶基因的身份很大程度上未知。在这里,我们描述了由PPARγ配体诱导的新型靶基因的分离和表征,称为 PGAR (与PPARγ血管生成素有关),该基因编码分泌蛋白的血管生成素家族的一个新成员。 PGAR的转录诱导遵循立即早期基因典型的快速过程,并且在没有蛋白质合成的情况下发生。 PGAR的表达主要定位于脂肪组织和胎盘,并且在肥胖的遗传模型中一直表达升高。激素依赖性脂肪细胞分化与PGAR转录物的戏剧性早期诱导相吻合。发现营养和瘦蛋白给药的改变在体内调节PGAR表达。综上所述,这些数据表明PGAR在调节全身性脂质代谢或葡萄糖稳态中的可能作用。

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