A synthetic antagonist for the peroxisome proliferator-activated receptor γ inhibits adipocyte differentiation
A synthetic antagonist for the peroxisome proliferator-activated receptor γ inhibits adipocyte differentiation
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DOI：
10.1074/jbc.275.3.1873
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发表时间：
2000-01-21
影响因子：
4.8
通讯作者：
Spiegelman, BM
中科院分区：
文献类型：
--
作者：
Wright, HM;Clish, CB;Spiegelman, BM
在寻找过氧化物酶体增殖体激活受体(PPAR) γ的天然配体时，我们发现了一种与该受体结合的合成化合物。双酚A二甘油酯醚（BADGE）是PPAR γ的配体，K-d（app）为100 μ m，该化合物没有明显的激活PPAR γ转录活性的能力；然而，BADGE可以拮抗激动剂配体（如罗格列酮）激活该受体转录和成脂作用的能力。BADGE还特异性阻断天然脂肪生成细胞系如3T3-L1和3T3-F442A细胞进行激素介导的细胞分化的能力。这些结果提供了第一个药理学证据，证明PPAR γ活性是激素诱导的脂肪细胞分化所必需的。
While searching for natural ligands for the peroxisome proliferator-activated receptor (PPAR) gamma, we identified a synthetic compound that binds to this receptor. Bisphenol A diglycidyl ether (BADGE) is a ligand for PPAR gamma with a K-d(app) of 100 mu M. This compound has no apparent ability to activate the transcriptional activity of PPAR gamma; however, BADGE can antagonize the ability of agonist ligands such as rosiglitazone to activate the transcriptional and adipogenic action of this receptor. BADGE also specifically blocks the ability of natural adipogenic cell lines such as 3T3-L1 and 3T3-F442A cells to undergo hormone-mediated cell differentiation. These results provide the first pharmacological evidence that PPAR gamma activity is required for the hormonally induced differentiation of adipogenic cells.