A PROSTAGLANDIN J(2) METABOLITE BINDS PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA AND PROMOTES ADIPOCYTE DIFFERENTIATION
A PROSTAGLANDIN J(2) METABOLITE BINDS PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA AND PROMOTES ADIPOCYTE DIFFERENTIATION
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DOI：
10.1016/0092-8674(95)90194-9
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发表时间：
1995-12-01
期刊：
影响因子：
64.5
通讯作者：
LEHMANN, JM
中科院分区：
文献类型：
--
作者：
KLIEWER, SA;LENHARD, JM;LEHMANN, JM
J(2)系列前列腺素（pg）在体内形成并对多种生物过程起作用。虽然大多数pg通过G蛋白偶联受体介导其作用，但J(2)系列pg的作用机制尚不清楚。在这里，我们报道了PGJ(2)及其衍生物是过氧化物酶体增殖体激活受体α和γ（分别为PPAR α和PPAR γ）的有效激活剂，它们是参与脂质稳态和脂肪细胞分化的孤儿核受体。PGJ(2)代谢物15-deoxy-Delta(12,14)-PGJ(2)直接与PPAR γ结合，促进C3H10T1/2成纤维细胞向脂肪细胞的有效分化。这些数据提供了强有力的证据，表明脂肪酸代谢物可以通过与PPAR γ直接相互作用而作为脂肪生成剂发挥作用，此外，还提示了J(2)系列pg的一种新的作用机制。
Prostaglandins (PGs) of the J(2) series form in vivo and exert effects on a variety of biological processes. While most PGs mediate their effects through G protein-coupled receptors, the mechanism of action for the J(2) series of PGs remains unclear. Here, we report that PGJ(2) and its derivatives are efficacious activators of peroxisome proliferator-activated receptors alpha and gamma (PPAR alpha and PPAR gamma, respectively), orphan nuclear receptors implicated in lipid homeostasis and adipocyte differentiation. The PGJ(2) metabolite 15-deoxy-Delta(12,14)-PGJ(2) binds directly to PPAR gamma and promotes efficient differentiation of C3H10T1/2 fibroblasts to adipocytes. These data provide strong evidence that a fatty acid metabolite can function as an adipogenic agent through direct interactions with PPAR gamma and, furthermore, suggest a novel mechanism of action for PGs of the J(2) series.