Whole transcriptome analysis of obese adipose tissue suggests u001kfc.1 as a potential regulator to glucose metabolism

LncRNAs are newly proposed key factors controlling brown adipogenesis and development, but their regulatory effect to white adipocyte is still merely understood. Deciphering the underlying mechanism could be a novel way to discovering potential targets of obesity. In the present study, the whole transcriptome of adipose tissues collected from obese individuals and control subjects were analyzed by HTA2.0. A stepwise network reconstruction strategy was proposed to explore lncRNA-related functional modules altered in obesity. A lncRNA named uc001kfc.1, which was recognized from the core network, was suggested to be down regulated in obesity group and might regulate glucose metabolism of adipocytes through PI3K/PTEN pathway. Our study highlighted the potential of lncRNA regulating glucose homeostasis in human adipose tissue from a global perspective, which would facilitate deeply understanding pathology of obesity as well as developing novel therapeutic targets. Our study was approved by the IRB of Hebei General Hospital and conducted according to the principles expressed in the Declaration of Helsinki. The use of these subjects was approved by the hospital’s Ethics Committee and all participants provided their written informed consents. All participants were recruited when they were hospitalized due to cholecystolithiasis. 11 obese patients and 22 controls were enrolled in this study. Separately, 6 and 5 subjects were randomly selected from the obesity and control group for microarray assay.

长链非编码RNA（Long non-coding RNA, LncRNAs）是新近被提出的调控棕色脂肪生成与发育的关键因子，但其对白色脂肪细胞的调控作用仍不甚明晰。解析其潜在调控机制，可为肥胖潜在治疗靶点的发掘提供全新思路。本研究通过HTA2.0芯片对肥胖患者与对照受试者的脂肪组织全转录组进行了分析，并提出了一种逐步网络重构策略，以探究肥胖状态下异常改变的长链非编码RNA相关功能模块。本研究从核心调控网络中筛选得到一条名为uc001kfc.1的长链非编码RNA，该RNA在肥胖组中呈下调表达，且可能通过PI3K/PTEN通路调控脂肪细胞的葡萄糖代谢。本研究从全局视角揭示了长链非编码RNA调控人体脂肪组织葡萄糖稳态的潜力，有助于深入阐明肥胖的病理机制，并为新型治疗靶点的开发提供支撑。本研究经河北总医院伦理审查委员会（Institutional Review Board, IRB）批准，严格遵循《赫尔辛基宣言》的伦理原则开展；受试者的使用亦获得医院伦理委员会批准，所有参与者均签署了书面知情同意书。所有参与者均因胆囊结石住院期间招募入组，本研究共纳入11名肥胖患者与22名对照受试者；分别从肥胖组与对照组中随机选取6名、5名受试者进行芯片检测。