15-脱氧-Δ12,14-前列腺素J2是脂肪细胞决定因子PPARγ的一种配体。

15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma.

作者信息

Forman B M, Tontonoz P, Chen J, Brun R P, Spiegelman B M, Evans R M

机构信息

Salk Institute for Biological Studies, La Jolla, California 92037, USA.

出版信息

Cell. 1995 Dec 1;83(5):803-12. doi: 10.1016/0092-8674(95)90193-0.

DOI:10.1016/0092-8674(95)90193-0

PMID:8521497

Abstract

Regulation of adipose cell mass is a critical homeostatic process in higher vertebrates. The conversion of fibroblasts into cells of the adipose lineage is induced by expression of the orphan nuclear receptor PPAR gamma. This suggests that an endogenous PPAR gamma ligand may be an important regulator of adipogenesis. By assaying arachidonate metabolites for their capacity to activate PPAR response elements, we have identified 15-deoxy-delta 12, 14-prostaglandin J2 as both a PPAR gamma ligand and an inducer of adipogenesis. Similarly, the thiazolidinedione class of antidiabetic drugs also bind to PPAR gamma and act as potent regulators of adipocyte development. Thus, adipogenic prostanoids and antidiabetic thiazolidinediones initiate key transcriptional events through a common nuclear receptor signaling pathway. These findings suggest a pivotal role for PPAR gamma and its endogenous ligand in adipocyte development and glucose homeostasis and as a target for intervention in metabolic disorders.

摘要

脂肪细胞量的调节是高等脊椎动物体内一个关键的稳态过程。成纤维细胞向脂肪谱系细胞的转化是由孤儿核受体PPARγ的表达所诱导的。这表明内源性PPARγ配体可能是脂肪生成的重要调节因子。通过检测花生四烯酸代谢产物激活PPAR反应元件的能力，我们鉴定出15-脱氧-Δ12,14-前列腺素J2既是一种PPARγ配体，也是脂肪生成的诱导剂。同样，噻唑烷二酮类抗糖尿病药物也与PPARγ结合，并作为脂肪细胞发育的有效调节剂。因此，促脂肪生成的前列腺素和抗糖尿病的噻唑烷二酮类药物通过共同的核受体信号通路启动关键的转录事件。这些发现表明PPARγ及其内源性配体在脂肪细胞发育和葡萄糖稳态中起关键作用，并可作为代谢紊乱干预的靶点。