Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
Int J Obes (Lond). 2012 Sep;36(9):1236-44. doi: 10.1038/ijo.2011.227. Epub 2011 Nov 29.
To investigate whether prohibitin (PHB) is a target gene in adipocyte differentiation and modulates insulin-induced adipocyte differentiation.
3T3-L1 preadipocyte overexpressing wild-type PHB and PHB mutant (lacking tyrosine-114 phosphorylation site) with or without insulin.
The treatment of 3T3-L1 fibroblasts with insulin or peroxisome proliferator-activated receptor-γ 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 ∼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.
In summary, we have identified PHB as an important protein in adipocyte differentiation.
研究抑素（PHB）是否为脂肪细胞分化的靶基因，并调节胰岛素诱导的脂肪细胞分化。
过表达野生型 PHB 和 PHB 突变体（缺乏酪氨酸 114 磷酸化位点）的 3T3-L1 前脂肪细胞，有或没有胰岛素。
胰岛素或过氧化物酶体增殖物激活受体-γ 激动剂处理 3T3-L1 成纤维细胞可导致 PHB 呈剂量和时间依赖性上调。对 PHB 启动子序列的分析表明，在翻译起始位点上游约 1kb 处存在潜在的胰岛素反应元件和 CCAAT/增强子结合蛋白转录元件。使用报告基因分析确定了这些位点的功能相关性。令人惊讶的是，瘦素也被发现可以调节 PHB。此外，PHB 在 3T3-L1 成纤维细胞中的过表达足以诱导脂肪生成。
综上所述，我们已经确定 PHB 是脂肪细胞分化中的一个重要蛋白。
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