Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0795.
Department of Dermatology, University of California, San Francisco, CA 94115.
Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6883-6889. doi: 10.1073/pnas.1920419117. Epub 2020 Mar 5.
Adipose tissue provides a defense against starvation and environmental cold. These dichotomous functions are performed by three distinct cell types: energy-storing white adipocytes, and thermogenic beige and brown adipocytes. Previous studies have demonstrated that exposure to environmental cold stimulates the recruitment of beige adipocytes in the white adipose tissue (WAT) of mice and humans, a process that has been extensively investigated. However, beige adipose tissue also develops during the peri-weaning period in mice, a developmental program that remains poorly understood. Here, we address this gap in our knowledge using genetic, imaging, physiologic, and genomic approaches. We find that, unlike cold-induced recruitment in adult animals, peri-weaning development of beige adipocytes occurs in a temperature- and sympathetic nerve-independent manner. Instead, the transcription factor B cell leukemia/lymphoma 6 (BCL6) acts in a cell-autonomous manner to regulate the commitment but not the maintenance phase of beige adipogenesis. Genome-wide RNA-sequencing (seq) studies reveal that BCL6 regulates a core set of genes involved in fatty acid oxidation and mitochondrial uncoupling, which are necessary for development of functional beige adipocytes. Together, our findings demonstrate that distinct transcriptional and signaling mechanisms control peri-weaning development and cold-induced recruitment of beige adipocytes in mammals.
脂肪组织为抵抗饥饿和环境寒冷提供了保护。这些截然不同的功能是由三种不同的细胞类型完成的：储存能量的白色脂肪细胞，以及产热的米色和棕色脂肪细胞。先前的研究表明，暴露于环境寒冷会刺激米色脂肪细胞在小鼠和人类的白色脂肪组织（WAT）中的募集，这一过程已经得到了广泛的研究。然而，米色脂肪组织在小鼠的围产期也会发育，这一发育过程仍然知之甚少。在这里，我们使用遗传、成像、生理和基因组方法来解决我们知识中的这一空白。我们发现，与成年动物中冷诱导的募集不同，围产期米色脂肪细胞的发育是一种温度和交感神经独立的方式。相反，转录因子 B 细胞白血病/淋巴瘤 6（BCL6）以细胞自主的方式发挥作用，调节米色脂肪生成的承诺阶段，但不调节维持阶段。全基因组 RNA 测序（seq）研究表明，BCL6 调节一组与脂肪酸氧化和线粒体解偶联相关的核心基因，这些基因对于功能性米色脂肪细胞的发育是必要的。总之，我们的研究结果表明，不同的转录和信号机制控制哺乳动物围产期发育和冷诱导的米色脂肪细胞募集。
