Forkhead box transcription factors have been shown to be involved in various developmental and differentiation processes. In particular, members of the FoxP family have been previously characterized in depth for their participation in the regulation of lung and neuronal cell differentiation and T-cell development and function; however, their role in adipocyte functionality has not yet been investigated. Here we report for the first time that FoxP4 is expressed at high levels in subcutaneous fat depots and in mature thermogenic adipocytes. Through molecular and gene expression analyses we revealed that FoxP4 is induced in response to thermogenic stimuli, both in vivo and in isolated cells, and is regulated directly by the heat shock factor HSF1 through a heat shock response element identified in the proximal promoter region of FoxP4. Further detailed analysis involving chromatin immunoprecipitation and luciferase assays demonstrated that FoxP4 directly controls the levels of UCP1, a key regulator of thermogenesis that uncouples fatty acid oxidation from ATP production. In addition, through our gain- and loss-of-function studies we showed that FoxP4 regulates the expression of a number of classic brown and beige fat genes and affects oxygen consumption in isolated adipocytes. Overall, our data demonstrate for the first time the novel role of FoxP4 in the regulation of thermogenic adipocyte functionality.

中文翻译：

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Forkhead Box 转录因子 FoxP4 调节脂肪细胞中的产热程序。

叉头盒转录因子已被证明参与各种发育和分化过程。尤其是，FoxP 家族的成员以前曾因参与调节肺和神经元细胞分化以及 T 细胞发育和功能而被深入研究。然而，尚未研究它们在脂肪细胞功能中的作用。在这里，我们首次报道 FoxP4 在皮下脂肪库和成熟的产热脂肪细胞中高水平表达。通过分子和基因表达分析，我们发现 FoxP4 在体内和分离的细胞中都是响应产热刺激而被诱导的，并且通过 FoxP4 近端启动子区域中鉴定的热激响应元件直接由热激因子 HSF1 调节. 涉及染色质免疫沉淀和荧光素酶测定的进一步详细分析表明，FoxP4 直接控制 UCP1 的水平，UCP1 是产热的关键调节剂，可将脂肪酸氧化与 ATP 产生分离。此外，通过我们的功能增益和功能丧失研究，我们发现 FoxP4 调节许多经典的棕色和米色脂肪基因的表达，并影响分离的脂肪细胞的耗氧量。总体而言，我们的数据首次证明了 FoxP4 在调节产热脂肪细胞功能中的新作用。通过我们的功能获得和功能丧失研究，我们发现 FoxP4 调节许多经典的棕色和米色脂肪基因的表达，并影响分离的脂肪细胞的耗氧量。总体而言，我们的数据首次证明了 FoxP4 在调节产热脂肪细胞功能中的新作用。通过我们的功能获得和功能丧失研究，我们发现 FoxP4 调节许多经典的棕色和米色脂肪基因的表达，并影响分离的脂肪细胞的耗氧量。总体而言，我们的数据首次证明了 FoxP4 在调节产热脂肪细胞功能中的新作用。