Obesity is a complex disease with multifactorial causes, and its prevalence is becoming a serious health crisis. For this reason, there is a crucial need to identify novel targets and players. With this aim in mind, we analyzed via RNA-sequencing the subcutaneous adipose tissue of normal weight and obesity-affected women, highlighting the differential expression in the two tissues. We specifically focused on long non-coding RNAs, as 6 of these emerged as dysregulated in the diseased-tissue (COL4A2-AS2, RPS21-AS, PELATON, ITGB2-AS1, ACER2-AS and CTEPHA1). For each of them, we performed both a thorough in silico dissection and in vitro validation, to predict their function during adipogenesis. We report the lncRNAs expression during adipose derived stem cells differentiation to adipocytes as model of adipogenesis and their potential modulation by adipogenesis-related transcription factors (C/EBPs and PPARγ). Moreover, inhibiting CTEPHA1 expression we investigated its impact on adipogenesis-related transcription factors, showing its significative dysregulation of C/EBPα expression. Lastly, we dissected the subcellular localization, pathway involvement and disease-correlation for coding differentially expressed genes. Together, these findings highlight a transcriptional deregulation at the basis of obesity, impacted by both coding and long non-coding RNAs.

肥胖是一种多因素的复杂疾病，其流行正在成为严重的健康危机。因此，迫切需要确定新的目标和参与者。考虑到这一目标，我们通过 RNA 测序分析了正常体重和受肥胖影响的女性的皮下脂肪组织，突出了两种组织中的差异表达。我们特别关注长链非编码 RNA，因为其中 6 个在患病组织中出现失调（COL4A2-AS2、RPS21-AS、PELATON、ITGB2-AS1、ACER2-AS 和 CTEPHA1）。对于它们中的每一个，我们都进行了彻底的计算机解剖和体外验证，以预测它们在脂肪生成过程中的功能. 我们报告了脂肪干细胞分化为脂肪细胞期间 lncRNAs 的表达，作为脂肪生成模型及其通过脂肪生成相关转录因子（C/EBPs 和 PPARγ）的潜在调节。此外，我们研究了抑制 CTEPHA1 表达对脂肪生成相关转录因子的影响，显示其显着失调 C/EBPα 表达。最后，我们剖析了编码差异表达基因的亚细胞定位、通路参与和疾病相关性。总之，这些发现突出了肥胖基础上的转录失调，受编码和长非编码 RNA 的影响。