Prohibitin has an important role in adipocyte differentiation

Prohibitin has an important role in adipocyte differentiation
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DOI:
10.1038/ijo.2011.227
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发表时间:
2012-09-01
影响因子:
4.9
通讯作者:
Mishra, S.
Mishra, S.
中科院分区:
医学2区
文献类型:
--
作者:
Ande, S. R.;Xu, Z.;Mishra, S.

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目的:探讨禁止素(PHB)是否为胰岛素诱导脂肪细胞分化的靶基因。设计:有或没有胰岛素的3T3-L1前脂肪细胞过表达野生型PHB和PHB突变体(缺乏酪氨酸-114磷酸化位点)。结果:用胰岛素或过氧化物酶体增殖物激活受体激动剂治疗3T3-L1成纤维细胞导致PHB呈剂量和时间依赖性上调。对PHB启动子序列的分析显示,在翻译起始位点上游约1kb处存在假定的胰岛素应答元件和CCAAT/增强子结合蛋白转录元件。这些位点的功能相关性通过报告基因测定来确定。令人惊讶的是,PHB也被发现受瘦素的调节。此外,PHB在3T3-L1成纤维细胞中过表达足以诱导脂肪形成。结论:综上所述,我们已经确定PHB是脂肪细胞分化的重要蛋白。
OBJECTIVE: To investigate whether prohibitin (PHB) is a target gene in adipocyte differentiation and modulates insulin-induced adipocyte differentiation.DESIGN: 3T3-L1 preadipocyte overexpressing wild-type PHB and PHB mutant (lacking tyrosine-114 phosphorylation site) with or without insulin.RESULTS: The treatment of 3T3-L1 fibroblasts with insulin or peroxisome proliferator-activated receptor-g agonist resulted in an upregulation of PHB in a dose-and time-dependent manner. An analysis of the PHB promoter sequence revealed the presence of putative insulin-response elements and CCAAT/enhancer-binding protein transcription elements within similar to 1 kb upstream of the translation initiation site. The functional relevance of these sites was determined using reporter gene assay. Surprisingly, PHB was also found to be regulated by leptin. Furthermore, the overexpression of PHB in 3T3-L1 fibroblasts was sufficient to induce adipogenesis.CONCLUSION: In summary, we have identified PHB as an important protein in adipocyte differentiation.