Enhancing brown fat activity and promoting white fat browning are attractive therapeutic strategies for treating obesity and associated metabolic disorders. To provide a comprehensive picture of the gene regulatory network in these processes, we conducted a series of transcriptome studies by RNA sequencing (RNA-seq) and quantified the mRNA and long noncoding RNA (lncRNA) changes during white fat browning (chronic cold exposure, beta-adrenergic agonist treatment, and intense exercise) and brown fat activation or inactivation (acute cold exposure or thermoneutrality, respectively). mRNA–lncRNA coexpression networks revealed dynamically regulated lncRNAs to be largely embedded in nutrient and energy metabolism pathways. We identified a brown adipose tissue–enriched lncRNA, lncBATE10, that was governed by the cAMP-cAMP response element-binding protein (Creb) axis and required for a full brown fat differentiation and white fat browning program. Mechanistically, lncBATE10 can decoy Celf1 from Pgc1α, thereby protecting Pgc1α mRNA from repression by Celf1. Together, these studies provide a comprehensive data framework to interrogate the transcriptomic changes accompanying energy homeostasis transition in adipose tissue.

增强棕色脂肪活性和促进白色脂肪褐变是用于治疗肥胖症和相关代谢紊乱的有吸引力的治疗策略。为了全面了解这些过程中的基因调控网络，我们通过RNA测序（RNA-seq）进行了一系列转录组研究，并对白色脂肪褐变（长期冷暴露， β-肾上腺素能激动剂治疗和剧烈运动）和棕色脂肪活化或失活（分别为急性冷暴露或热中性）。mRNA–lncRNA共表达网络揭示了动态调节的lncRNA，主要嵌入营养和能量代谢途径中。我们确定了富含棕色脂肪组织的lncRNA，lncBATE10，它由cAMP-cAMP反应元件结合蛋白（Creb）轴控制，是完整的棕色脂肪分化和白色脂肪褐变程序所必需的。从机制上讲，lncBATE10可以将Celf1与Pgc1α诱骗，从而保护Pgc1αmRNA不受Celf1的抑制。总之，这些研究提供了一个综合的数据框架，可以询问脂肪组织中能量稳态转换伴随的转录组变化。