Long non-coding RNAs associated with metabolic traits in human white adipose tissue

Long non-coding RNAs (lncRNAs) belong to a recently discovered class of molecules proposed to regulate various cellular processes. Here, we systematically analyzed their expression in human subcutaneous white adipose tissue (WAT) and found that a limited set was differentially expressed in either obesity or the insulin resistance that usually follows obesity. Two lncRNAs herein termed adipocyte-specific metabolic related lncRNAs 1(ASMER-1) and ASMER-2 were enriched in adipocytes and regulated by both obesity and insulin resistance. Knockdown of either ASMER-1or ASMER-2 by antisense oligonucleotides using in vitro differentiated human adipocytes altered lipolysis and adiponectin secretion, respectively. The observed effects could be attributed to changes in the expression of genes controlling inflammation and lipid metabolism. Our data demonstrate that lncRNAs are modulators of the metabolic and endocrine functions in fat cells and also provide an emerging link between WAT and common metabolic conditions. Overall design: Human adipose tissues mRNA profiles of obese (13) and lean (15) subjects were generated by deep sequencing using Illumina 2000.

长链非编码核糖核酸（long non-coding RNAs, lncRNAs）属于近年发现的一类被认为可调控多种细胞进程的分子。本研究系统性分析了其在人类皮下白色脂肪组织（subcutaneous white adipose tissue, WAT）中的表达情况，发现仅有有限的一部分长链非编码核糖核酸在肥胖或通常伴随肥胖出现的胰岛素抵抗中存在差异表达。本研究中命名为脂肪细胞特异性代谢相关长链非编码核糖核酸1（ASMER-1）与ASMER-2的两种长链非编码核糖核酸，在脂肪细胞中富集表达，且同时受肥胖与胰岛素抵抗的调控。通过反义寡核苷酸（antisense oligonucleotides）在体外分化的人脂肪细胞中敲低ASMER-1或ASMER-2，可分别改变脂解过程与脂联素分泌水平。观测到的这些效应可归因于调控炎症与脂质代谢的基因表达变化。本研究数据表明，长链非编码核糖核酸是脂肪细胞代谢与内分泌功能的调控因子，同时也为皮下白色脂肪组织与常见代谢疾病之间的关联提供了新的研究线索。
实验整体设计：通过Illumina 2000平台进行深度测序，获取了13名肥胖受试者与15名消瘦受试者的人类脂肪组织mRNA表达谱。