Distinct Roles of Transcription Factors KLF4, Krox20, and Peroxisome Proliferator-Activated Receptor γ in Adipogenesis
Distinct Roles of Transcription Factors KLF4, Krox20, and Peroxisome Proliferator-Activated Receptor γ in Adipogenesis
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DOI：
10.1128/mcb.00554-16
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发表时间：
2017-01-01
影响因子：
5.3
通讯作者：
Ge, Kai
中科院分区：
文献类型：
--
作者：
Park, Young-Kwon;Wang, Limin;Ge, Kai
我们关于脂肪生成的大部分知识来自于前脂肪细胞分化的细胞培养模型。成脂鸡尾酒处理融合的前脂肪细胞，在几分钟内激活转录因子(TF)、糖皮质激素受体(GR)和CREB，并在几小时内增加TFS C/EBPβ、C/EBP Delta、KLF4和Krox20的表达，从而诱导脂肪生成。所有这些转录因子都被证明能够在培养中促进脂肪生成，当它们过度表达时。然而，目前尚不清楚内源性KLF4和Krox20是否是培养和体内脂肪形成所必需的。利用条件性基因敲除小鼠和衍生的白色和棕色前脂肪细胞，我们证明内源性KLF4和Krox20对于培养中的脂肪生成和小鼠棕色脂肪组织的发育是必不可少的。相比之下，主要的成脂因子过氧化物酶体增殖物激活受体伽马(PPAR伽马)是必不可少的。这些结果对现有的脂肪生成早期阶段转录调控模型提出了挑战，突出了体内脂肪生成研究的必要性。
Much of our knowledge on adipogenesis comes from cell culture models of preadipocyte differentiation. Adipogenesis is induced by treating confluent preadipocytes with the adipogenic cocktail, which activates transcription factors (TFs) glucocorticoid receptor (GR) and CREB within minutes and increases expression of TFs C/EBP beta, C/EBP delta, KLF4, and Krox20 within hours. All of these TFs have been shown to be capable of promoting adipogenesis in culture when they are overexpressed. However, it has remained unclear whether endogenous KLF4 and Krox20 are required for adipogenesis in culture and in vivo. Using conditional knockout mice and derived white and brown preadipocytes, we show that endogenous KLF4 and Krox20 are dispensable for adipogenesis in culture and for brown adipose tissue development in mice. In contrast, the master adipogenic TF peroxisome proliferator-activated receptor gamma (PPAR gamma) is essential. These results challenge the existing model on transcriptional regulation in the early phase of adipogenesis and highlight the need of studying adipogenesis in vivo.