Given the high and increasing prevalence of obesity and associated disorders, such as type-2 diabetes, it is important to understand the mechanisms that regulate lipid storage and the differentiation of fat cells, a process termed adipogenesis. Using the well-established mouse 3T3-L1 in vitro model of adipogenesis, we refine how the induction of two key adipogenic transcription factors, CCAAT/enhancer-binding proteins (C/EBPs) β and ẟ are regulated during early adipogenesis. We identify, in the gene promoters of Cebpb and Cebpd, the DNA response elements responsible for binding transcription factors that are activated by cAMP or glucocorticoids. We also show that mitogen-activated protein kinase (MAPK)-interacting kinase 2 (MNK2; Mknk2), which plays a distinct role in diet-induced obesity, is induced during early adipogenesis and identify the functional DNA response elements responsible for regulating its expression. Mknk2 expression is maintained in differentiated 3T3-L1 adipocytes and is expressed at high levels across a range of mouse adipose tissue depots. Together, these new insights help to clarify the transcriptional program of early adipogenesis and identify Mknk2 as one of potentially many genes up-regulated during adipogenesis.

中文翻译：

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识别早期脂肪形成过程中调节CCAAT /增强子结合蛋白（C / EBP）β和δ表达的DNA反应元件

鉴于肥胖症和相关疾病（例如2型糖尿病）的患病率不断提高，重要的是要了解调节脂质储存和脂肪细胞分化的机制，这一过程被称为脂肪形成。使用建立良好的小鼠脂肪形成体外3T3-L1体外模型，我们完善了如何在早期脂肪形成过程中调节两个关键的脂肪形成转录因子CCAAT /增强子结合蛋白（C / EBPs）β和the的诱导。我们在Cebpb和Cebpd的基因启动子中确定负责结合由cAMP或糖皮质激素激活的转录因子的DNA反应元件。我们还显示，在饮食诱导的肥胖中起独特作用的促分裂原激活蛋白激酶（MAPK）相互作用激酶2（MNK2; Mknk2），在早期脂肪形成过程中被诱导，并识别负责调节其表达的功能性DNA反应元件。Mknk2表达在分化的3T3-L1脂肪细胞中得以维持，并在一系列小鼠脂肪组织贮库中以高水平表达。总之，这些新见解有助于阐明早期脂肪形成的转录程序，并将Mknk2鉴定为脂肪形成过程中可能上调的许多基因之一。