Clenbuterol inhibits SREBP-1c expression by activating CREB1.
Clenbuterol inhibits SREBP-1c expression by activating CREB1.
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DOI：
10.5483/bmbrep.2007.40.4.525
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发表时间：
2007-07
期刊：
影响因子：
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通讯作者：
Lei Zhou;Yixing Li;Tao Nie;S. Feng;Ji-hong Yuan;Huaping Chen;Zaiqing Yang
中科院分区：
文献类型：
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作者：
Lei Zhou;Yixing Li;Tao Nie;S. Feng;Ji-hong Yuan;Huaping Chen;Zaiqing Yang
作为一种β（2）-肾上腺素能激动剂，克仑特罗减少体脂，但这一过程的分子机制尚不清楚。在本研究中，我们用克伦特罗处理293 T和L-02细胞，发现克伦特罗下调SREBP-1c的表达，上调CREB 1的表达。考虑到SREBP-1c具有调节多种脂肪生成酶转录的功能，我们认为SREBP-1c的下调是克伦特罗降低体脂的原因。许多研究发现，克伦特罗显着增加细胞内cAMP水平，因此，我们也研究CREB 1是否参与这一过程。我们的实验数据表明，CREB 1过表达抑制SREBP-1c的转录，这种作用被CREB 2拮抗，CREB 2是CREB 1的竞争性抑制剂。此外，由于PPARs能够抑制SREBP-1c转录，我们研究了克伦特罗和CREB 1是否通过涉及PPAR激活的途径发挥作用。然而，我们的研究结果表明，克伦特罗或CREB 1过表达抑制PPARs在293 T和L-02细胞中的转录，这表明它们以其他方式损害SREBP-1c的表达。
As a beta(2)-adrenergic agonist, clenbuterol decreases body fat, but the molecular mechanism underlying this process is unclear. In the present study, we treated 293T and L-02 cells with clenbuterol and found that clenbuterol downregulates SREBP-1c expression and upregulates CREB1 expression. Considering SREBP-1c has the function of regulating the transcription of several lipogenic enzymes, we considered that the downregulation of SREBP-1c is responsible for body fat reduction by clenbuterol. Many previous studies have found that clenbuterol markedly increases intracellular cAMP levels, therefore, we also investigated whether CREB1 is involved in this process. The data from our experiments indicate that CREB1 overexpression inhibits SREBP-1c transcription, and that this action is antagonized by CREB2, a competitive inhibitor of CREB1. Furthermore, since PPARs are able to repress SREBP-1c transcription, we investigated whether clenbuterol and CREB1 function via a pathway involving PPAR activation. However, our results showed that clenbuterol or CREB1 overexpression suppressed PPARs transcription in 293T and L-02 cells, which suggested that they impair SREBP-1c expression in other ways.