Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor γ isoforms
Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor γ isoforms
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DOI：
10.1074/jbc.m206950200
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发表时间：
2002-11-01
影响因子：
4.8
通讯作者：
Spiegelman, BM
中科院分区：
文献类型：
--
作者：
Mueller, E;Drori, S;Spiegelman, BM
d过氧化物酶体增殖物激活受体（PPAR）γ是一种核受体，是脂肪形成的关键调节因子，存在于通过选择性剪接产生的两种亚型中，即PPARgamma 1和PPARgamma 2。对每种异构体刺激脂肪分化的能力的研究产生了模糊的结果，部分原因是PPARgamma刺激其自身的表达。因此，我们已经进行了正式的遗传分析，使用PPARgamma空成纤维细胞系，以评估在脂肪形成中的每一个单独的异构体的具体作用。我们在这里表明，PPARgamma 1和PPARgamma 2都有内在的能力，刺激强大的脂肪形成。由PPARgamma 1或PPARgamma 2刺激的脂肪细胞表达相似的基因谱，并显示出对胰岛素的相似反应。然而，响应于低配体浓度，PPARgamma 2显示出在数量上更大的诱导脂肪形成的能力。涉及共激活因子结合和转录测定的分析表明，PPARgamma 2具有增强的结合DRIP/TRAP复合物组分的能力，DRIP/TRAP复合物是脂肪分化所需的共激活因子。
dPeroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor that is a key regulator of adipogenesis and is present in two isoforms generated by alternative splicing, PPARgamma1 and PPARgamma2. Studies of the ability of each isoform to stimulate fat differentiation have yielded ambiguous results, in part because PPARgamma stimulates its own expression. We have thus undertaken a formal genetic analysis using PPARgamma-null fibroblast cell lines to assess the specific role of each individual isoform in adipogenesis. We show here that both PPARgamma1 and PPARgamma2 have the intrinsic ability to stimulate robust adipogenesis. Adipose cells stimulated by either PPARgamma1 or PPARgamma2 express a similar gene profile and show similar responses to insulin. However, in response to low ligand concentrations, PPARgamma2 shows a quantitatively greater ability to induce adipogenesis. Analyses involving coactivator binding and transcriptional assays indicate that PPARgamma2 has an enhanced ability to bind components of the DRIP/TRAP complex, coactivators required for fat differentiation.