Bai Zhiqiang, Chai Xiao-Ran, Yoon Myeong Jin, Kim Hye-Jin, Lo Kinyui Alice, Zhang Zhi-Chun, Xu Dan, Siang Diana Teh Chee, Walet Arcinas Camille Esther, Xu Shao-Hai, Chia Sook-Yoong, Chen Peng, Yang Hongyuan, Ghosh Sujoy, Sun Lei
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
PLoS Biol. 2017 Aug 1;15(8):e2002176. doi: 10.1371/journal.pbio.2002176. eCollection 2017 Aug.
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棕色化是治疗肥胖及相关代谢紊乱的有吸引力的治疗策略。为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，并对白色脂肪棕色化（慢性冷暴露、β-肾上腺素能激动剂治疗和剧烈运动）以及棕色脂肪激活或失活（分别为急性冷暴露或热中性）过程中的mRNA和长链非编码RNA（lncRNA）变化进行了定量分析。mRNA-lncRNA共表达网络显示，动态调控的lncRNAs主要嵌入营养和能量代谢途径。我们鉴定出一种富含棕色脂肪组织的lncRNA，即lncBATE10，它受cAMP- cAMP反应元件结合蛋白（Creb）轴调控，是棕色脂肪完全分化和白色脂肪棕色化程序所必需的。从机制上讲，lncBATE10可以从Pgc1α上诱捕Celf1，从而保护Pgc1α mRNA不被Celf1抑制。总之，这些研究提供了一个全面的数据框架，以探究脂肪组织中伴随能量稳态转变的转录组变化。
