Foxp1 controls brown/beige adipocyte differentiation and thermogenesis through regulating β3-AR desensitization
Foxp1 controls brown/beige adipocyte differentiation and thermogenesis through regulating β3-AR desensitization
复制标题
Foxp1通过调节β3-AR脱敏来控制棕色/米色脂肪细胞分化和产热
DOI：
10.1038/s41467-019-12988-8
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发表时间：
2019-11-07
影响因子：
16.6
通讯作者：
Guo, Xizhi
中科院分区：
文献类型：
--
作者：
Liu, Pei;Huang, Sixia;Guo, Xizhi
β-肾上腺素能受体（β-AR）信号传导是控制褐色或米色脂肪细胞中的适应性产热的途径。在这里，我们调查的生物学作用的转录因子Foxp 1棕色/米色脂肪细胞分化和产热。脂肪特异性缺失Foxp 1导致棕色脂肪活性增加和白色脂肪组织的布朗宁程序。Foxp 1缺陷小鼠表现出增加的能量消耗，并免受饮食诱导的肥胖和胰岛素抵抗的影响。因此，Foxp 1在脂肪细胞中的过表达损害了适应性产热并促进了饮食诱导的肥胖。在来自两个品系小鼠的棕色/米色脂肪细胞中观察到β 3-肾上腺素能受体（β 3-AR）丰度的稳健变化。在分子水平上，Foxp 1直接抑制β 3-AR的转录并调节其脱敏行为。总之，我们的研究结果揭示Foxp 1作为棕色/米色脂肪细胞分化和产热的主要转录抑制因子，并为其靶向和治疗肥胖提供了重要线索。
beta-Adrenergic receptor (beta-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 beta 3-adrenergic receptor (beta 3-AR) is observed in brown/beige adipocytes from both lines of mice. Molecularly, Foxp1 directly represses beta 3-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.