Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore.
Nat Commun. 2018 Apr 6;9(1):1329. doi: 10.1038/s41467-018-03754-3.
Obesity has emerged as an alarming health crisis due to its association with metabolic risk factors such as diabetes, dyslipidemia, and hypertension. Recent work has demonstrated the multifaceted roles of lncRNAs in regulating mouse adipose development, but their implication in human adipocytes remains largely unknown. Here we present a catalog of 3149 adipose active lncRNAs, of which 909 are specifically detected in brown adipose tissue (BAT) by performing deep RNA-seq on adult subcutaneous, omental white adipose tissue and fetal BATs. A total of 169 conserved human lncRNAs show positive correlation with their nearby mRNAs, and knockdown assay supports a role of lncRNAs in regulating their nearby mRNAs. The knockdown of one of those, lnc-dPrdm16, impairs brown adipocyte differentiation in vitro and a significant reduction of BAT-selective markers in in vivo. Together, our work provides a comprehensive human adipose catalog built from diverse fat depots and establishes a roadmap to facilitate the discovery of functional lncRNAs in adipocyte development.
肥胖已成为一个令人震惊的健康危机，因为它与代谢风险因素有关，如糖尿病、血脂异常和高血压。最近的研究表明，lncRNAs 在调节小鼠脂肪发育中具有多方面的作用，但它们在人类脂肪细胞中的作用在很大程度上尚不清楚。在这里，我们提供了一个包含 3149 个脂肪组织活性 lncRNAs 的目录，其中 909 个是通过对成年皮下、网膜白色脂肪组织和胎儿棕色脂肪组织进行深度 RNA-seq 检测到的棕色脂肪组织（BAT）中特异性检测到的。总共 169 个保守的人类 lncRNAs 与其附近的 mRNAs 呈正相关，并且敲低实验支持 lncRNAs 在调节其附近 mRNAs 中的作用。其中一个 lnc-dPrdm16 的敲低会损害体外棕色脂肪细胞分化，并且在体内显著降低 BAT 选择性标记物。总之，我们的工作提供了一个来自不同脂肪组织的全面的人类脂肪目录，并为发现脂肪细胞发育中功能性 lncRNAs 提供了一个路线图。
