PPARgamma induces the insulin-dependent glucose transporter GLUT4 in the absence of C/EBPalpha during the conversion of 3T3 fibroblasts into adipocytes.
PPARgamma induces the insulin-dependent glucose transporter GLUT4 in the absence of C/EBPalpha during the conversion of 3T3 fibroblasts into adipocytes.
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DOI：
10.1172/jci1244
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
Zhidan Wu;Yuhong Xie;R. Morrison;N. Bucher;S. Farmer
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文献类型：
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作者：
Zhidan Wu;Yuhong Xie;R. Morrison;N. Bucher;S. Farmer
为了确定在脂肪形成期间控制GLUT 4表达的分子机制，使用在四环素应答诱导型（C/EBP）或组成型逆转录病毒（PPARgamma）表达系统的控制下异位表达不同脂肪形成转录因子（C/EBP β、C/EBP δ、C/EBP α和PPARgamma）的NIH-3 T3成纤维细胞。在暴露于地塞米松和PPARgamma配体环格列酮（一种噻唑烷二酮）的细胞中，C/EBP β（β 2细胞系）、C/EBP β与C/EBP δ（β/δ 39细胞系）、C/EBP α（α 1细胞系）或PPARgamma（Pgamma 2细胞系）的产生增强，导致GLUT 4 mRNA以及成脂基因程序的其他成员（包括aP 2和adipsin）表达。将我们的研究集中在β/δ 39细胞上，我们已经证明，在地塞米松存在下，C/EBP β沿着C/EBP δ诱导PPARgamma、adipsin和aP 2 mRNA的产生;然而，GLUT 4 mRNA仅在暴露于环格列酮的细胞中表达。此外，β/δ 39成纤维细胞中配体活化形式的PPARgamma的增强表达刺激GLUT 4蛋白的合成，并产生直接响应胰岛素而摄取葡萄糖的脂肪细胞群。在刺激脂肪形成程序的条件下，C/EBPalpha在β/δ 39细胞中不表达。这一观察结果表明，单独或与C/EBP β和C/EBP δ组合的PPARgamma能够激活GLUT 4基因表达。
To define the molecular mechanisms that control GLUT4 expression during adipogenesis, NIH-3T3 fibroblasts ectopically expressing different adipogenic transcription factors (C/EBPbeta, C/EBPdelta, C/EBPalpha, and PPARgamma) under the control of a tetracycline-responsive inducible (C/EBPs) or a constitutive retroviral (PPARgamma) expression system were used. Enhanced production of C/EBPbeta (beta2 cell line), C/EBPbeta together with C/EBPdelta (beta/delta39 cell line), C/EBPalpha (alpha1 cell line), or PPARgamma (Pgamma2 cell line) in cells exposed to dexamethasone and the PPARgamma ligand ciglitazone (a thiazolidinedione) resulted in expression of GLUT4 mRNA as well as other members of the adipogenic gene program, including aP2 and adipsin. Focusing our studies on the beta/delta39 cells, we have demonstrated that C/EBPbeta along with C/EBPdelta in the presence of dexamethasone induces PPARgamma, adipsin, and aP2 mRNA production; however, GLUT4 mRNA is only expressed in cells exposed to ciglitazone. In addition, enhanced expression of a ligand-activated form of PPARgamma in the beta/delta39 fibroblasts stimulates synthesis of GLUT4 protein and gives rise to a population of adipocytic cells that take up glucose in direct response to insulin. C/EBPalpha is not expressed in the beta/delta39 cells under conditions that stimulate the adipogenic program. This observation suggests that PPARgamma alone or in combination with C/EBPbeta and C/EBPdelta is capable of activating GLUT4 gene expression.