Beige adipocytes possess a discrete developmental origin and notable plasticity in thermogenic capacity in response to various environmental cues. But the transcriptional machinery controlling beige adipocyte development and thermogenesis remains largely unknown. By analyzing beige adipocyte-specific knockout mice, we identified a transcription factor, Forkhead Box P4 (FOXP4) that differentially governs beige adipocyte differentiation and activation. Depletion of Foxp4 caused a decline in the frequency of beige preadipocytes by switching their cell fate towards fibroblastic cells at the expense of beige adipocytes. However, we observed that ablation of Foxp4 in differentiated adipocytes profoundly potentiated their thermogenesis upon cold exposure. Of note, the outcome of Foxp4-deficiency on UCP1-mediated thermogenesis was confined to beige adipocytes, rather than to brown adipocytes. Taken together, we submit that FOXP4 primes beige adipocyte cell fate commitment and differentiation by potent transcriptional repression of the thermogenic program.

中文翻译：

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FOXP4 差异控制冷诱导的米色脂肪细胞分化和产热

米色脂肪细胞具有离散的发育起源和显着的生热能力可塑性，以响应各种环境线索。但是控制米色脂肪细胞发育和产热的转录机制在很大程度上仍然未知。通过分析米色脂肪细胞特异性基因敲除小鼠，我们确定了一种转录因子 Forkhead Box P4 (FOXP4)，它可以差异性地控制米色脂肪细胞的分化和激活。Foxp4 的消耗通过以米色脂肪细胞为代价将其细胞命运转向成纤维细胞而导致米色前脂肪细胞的频率下降。然而，我们观察到分化脂肪细胞中Foxp4 的消融极大地增强了它们在冷暴露时的产热。值得注意的是，结果Foxp4对 UCP1 介导的产热的缺陷仅限于米色脂肪细胞，而不是棕色脂肪细胞。总之，我们认为 FOXP4 通过对产热程序的有效转录抑制来启动米色脂肪细胞命运承诺和分化。