The forkhead transcription factor FoxC2 inhibits white adipocyte differentiation
The forkhead transcription factor FoxC2 inhibits white adipocyte differentiation
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DOI：
10.1074/jbc.m402197200
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发表时间：
2004-10-08
影响因子：
4.8
通讯作者：
Farmer, SR
中科院分区：
文献类型：
--
作者：
Davis, KE;Moldes, M;Farmer, SR
在这项研究中，我们发现，FoxC 2的表达阻断了3 T3-L1前脂肪细胞在地塞米松，异丁基甲基黄嘌呤和胰岛素存在下进行脂肪形成的能力。这种阻滞的特征在于与成熟脂肪细胞功能相关的蛋白质表达的广泛降低，最显著的是C/EBPalpha、脂联素、周脂蛋白和脂肪特异性脂肪酸结合蛋白FABP 4/aP 2。由于这些蛋白质的表达位于PPARgamma的下游，我们在瑞士小鼠成纤维细胞中过表达PPARgamma以促进脂肪细胞分化。我们发现FoxC 2阻断了PPARgamma诱导成脂基因表达的能力，以响应细胞暴露于地塞米松、异丁基甲基黄嘌呤、胰岛素和PPARgamma配体。有趣的是，在促进最大PPARgamma活性的条件下，aP 2的表达逃避了FoxC 2的抑制作用。相比之下，FoxC 2抑制C/EBPalpha，perilipin和脂联素的表达，即使在有效的PPARgamma配体的存在下。最后，我们表明FoxC 2不影响PPARgamma结合或反式激活PPARgamma反应元件的能力。这些数据表明，FoxC 2通过抑制PPARgamma促进脂肪形成基因亚组表达的能力来阻断脂肪形成。
In this study, we show that expression of FoxC2 blocks the capacity of 3T3-L1 preadipocytes to undergo adipogenesis in the presence of dexamethasone, isobutylmethylxanthine, and insulin. This block is characterized by an extensive decrease in the expression of proteins associated with the function of the mature fat cell, most notably C/EBPalpha, adiponectin, perilipin, and the adipose-specific fatty acid-binding protein, FABP4/aP2. Since the expression of these proteins lies downstream of PPARgamma, we overexpressed PPARgamma in Swiss mouse fibroblasts to promote adipocyte differentiation. We show that FoxC2 blocks the ability of PPARgamma to induce adipogenic gene expression in response to exposure of the cells to dexamethasone, isobutylmethylxanthine, insulin, and a PPARgamma ligand. Interestingly, the expression of aP2 escapes the inhibitory action of FoxC2 under conditions that promote maximum PPARgamma activity. In contrast, FoxC2 inhibits the expression of C/EBPalpha, perilipin, and adiponectin even in the presence of potent PPARgamma ligands. Finally, we show that FoxC2 does not affect the ability of PPARgamma to bind to or transactivate from a PPARgamma response element. These data suggest that FoxC2 blocks adipogenesis by inhibiting the capacity of PPARgamma to promote the expression of a subset of adipogenic genes.