β-Adrenergic receptor (β-AR) signaling is a pathway controlling adaptive thermogenesis in brown or beige adipocytes. Here we investigate the biological roles of the transcription factor Foxp1 in brown/beige adipocyte differentiation and thermogenesis. Adipose-specific deletion of Foxp1 leads to an increase of brown adipose activity and browning program of white adipose tissues. The Foxp1-deficient mice show an augmented energy expenditure and are protected from diet-induced obesity and insulin resistance. Consistently, overexpression of Foxp1 in adipocytes impairs adaptive thermogenesis and promotes diet-induced obesity. A robust change in abundance of the β3-adrenergic receptor (β3-AR) is observed in brown/beige adipocytes from both lines of mice. Molecularly, Foxp1 directly represses β3-AR transcription and regulates its desensitization behavior. Taken together, our findings reveal Foxp1 as a master transcriptional repressor of brown/beige adipocyte differentiation and thermogenesis, and provide an important clue for its targeting and treatment of obesity.

中文翻译：

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Foxp1通过调节β3-AR脱敏来控制棕色/米色脂肪细胞的分化和生热。

β-肾上腺素能受体（β-AR）信号传导是控制棕色或米色脂肪细胞中适应性生热的途径。在这里，我们调查转录因子Foxp1在棕色/米色脂肪细胞分化和生热中的生物学作用。特定于脂肪的Foxp1缺失会导致棕色脂肪活性的增加和白色脂肪组织的褐变程序。缺乏Foxp1的小鼠显示出增加的能量消耗，并免受饮食诱导的肥胖和胰岛素抵抗。一致地，脂肪细胞中Foxp1的过表达损害了适应性生热作用，并促进了饮食引起的肥胖。在两只小鼠的棕色/米色脂肪细胞中都观察到了β3-肾上腺素能受体（β3-AR）丰度的强烈变化。在分子上，Foxp1直接抑制β3-AR转录并调节其脱敏行为。