Department of Biosciences and Nutrition, Novum, Floor 7, Karolinska Institutet, 141 86 Stockholm, Sweden.
Department of Medicine, Karolinska Institutet, C2-94, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden.
EBioMedicine. 2018 Apr;30:248-260. doi: 10.1016/j.ebiom.2018.03.010. Epub 2018 Mar 15.
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 obesity and/or the insulin resistant state. Two lncRNAs herein termed adipocyte-specific metabolic related lncRNAs, ASMER-1 and ASMER-2 were enriched in adipocytes and regulated by both obesity and insulin resistance. Knockdown of either ASMER-1 or ASMER-2 by antisense oligonucleotides in in vitro differentiated human adipocytes revealed that both genes regulated adipogenesis, lipid mobilization and adiponectin secretion. The observed effects could be attributed to crosstalk between ASMERs and genes within the master regulatory pathways for adipocyte function including PPARG and INSR. Altogether, our data demonstrate that lncRNAs are modulators of the metabolic and secretory functions in human fat cells and provide an emerging link between WAT and common metabolic conditions.
长非编码 RNA(lncRNAs)属于最近发现的一类分子,据推测可调节各种细胞过程。在这里,我们系统地分析了它们在人体皮下白色脂肪组织(WAT)中的表达,发现它们在肥胖和/或胰岛素抵抗状态下的表达存在差异。我们在此将两个 lncRNA 称为脂肪细胞特异性代谢相关 lncRNA,即 ASMER-1 和 ASMER-2,它们在脂肪细胞中富集,并受到肥胖和胰岛素抵抗的调节。在体外分化的人类脂肪细胞中用反义寡核苷酸敲低任一 ASMER-1 或 ASMER-2,发现这两个基因均调节脂肪生成、脂动员和脂联素分泌。观察到的效应可归因于 ASMER 与脂肪细胞功能的主调控途径(包括 PPARG 和 INSR)内基因之间的串扰。总的来说,我们的数据表明 lncRNAs 是人类脂肪细胞代谢和分泌功能的调节剂,并为 WAT 和常见代谢疾病之间提供了一个新兴的联系。