Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0795.
Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0795;
Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):17071-17080. doi: 10.1073/pnas.1907308116. Epub 2019 Aug 2.
Brown adipocytes provide a metabolic defense against environmental cold but become dormant as mammals habituate to warm environments. Although dormancy is a regulated response in brown adipocytes to environmental warmth, its transcriptional mechanisms and functional importance are unknown. Here, we identify B cell leukemia/lymphoma 6 (BCL6) as a critical regulator of dormancy in brown adipocytes but not for their commitment, differentiation, or cold-induced activation. In a temperature-dependent manner, BCL6 suppresses apoptosis, fatty acid storage, and coupled respiration to maintain thermogenic fitness during dormancy. Mechanistically, BCL6 remodels the epigenome of brown adipocytes to enforce brown and oppose white adipocyte cellular identity. Thus, unlike other thermogenic regulators, BCL6 is specifically required for maintaining thermogenic fitness when mammals acclimate to environmental warmth.
棕色脂肪细胞为哺乳动物适应温暖环境提供了一种代谢防御机制，但随着哺乳动物逐渐适应温暖的环境，棕色脂肪细胞会进入休眠状态。虽然休眠是棕色脂肪细胞对环境温暖的一种调节反应，但它的转录机制和功能意义尚不清楚。在这里，我们发现 B 细胞淋巴瘤/白血病 6（BCL6）是棕色脂肪细胞休眠的关键调节因子，但不是其分化或冷诱导激活所必需的。BCL6 以温度依赖的方式抑制细胞凋亡、脂肪酸储存和偶联呼吸，以维持休眠期间的产热适应性。从机制上讲，BCL6 重塑了棕色脂肪细胞的表观基因组，以维持棕色脂肪细胞的特性并抑制其向白色脂肪细胞转化。因此，与其他产热调节因子不同，BCL6 是哺乳动物适应环境温暖时维持产热适应性所必需的。
