Local hypoxia has recently been reported to occur in the white adipose tissue (WAT) microenvironment during obesity. Adipocytes have a unique life cycle that reflects the different stages of adipogenesis in the WAT niche. Long non-coding RNAs (lncRNAs) play an important role in the cellular response to hypoxia. However, the differentially hypoxic responses of preadipocytes during adipogenesis and the potential role of lncRNAs in this process remain to be elucidated. Here, we evaluated the differentially hypoxic responses of primary hamster preadipocytes during adipogenesis and analyzed mRNA and lncRNA expression in same Ribo-Zero RNA-seq libraries. Hypoxia induced HIF-1α protein during adipogenesis and caused divergent changes of cell phenotypes. A total of 10,318 mRNAs were identified to be expressed in twenty libraries (five timepoints), and 3,198 differentially expressed mRNAs (DE mRNAs) were detected at five timepoints (hypoxia vs. normoxia). Functional enrichment analysis revealed the shared and specific hypoxia response pathways in the different stages of adipogenesis. Hypoxia differentially modulated the expression profile of adipose-associated genes, including adipokines, lipogenesis, lipolysis, hyperplasia, hypertrophy, inflammatory, and extracellular matrix. We also identified 4,296 lncRNAs that were expressed substantially and detected 1,431 DE lncRNAs at five timepoints. Two, 3, 5, 13, and 50 DE mRNAs at D0, D1, D3, D7, and D11, respectively, were highly correlated and locus-nearby DE lncRNAs and mainly involved in the cell cycle, vesicle-mediated transport, and mitochondrion organization. We identified 28 one-to-one lncRNA-mRNA pairs that might be closely related to adipocyte functions, such as ENSCGRT00015041780-Hilpda, TU2105-Cdsn, and TU17588-Ltbp3. These lncRNAs may represent the crucial regulation axis in the cellular response to hypoxia during adipogenesis. This study dissected the effects of hypoxia in the cell during adipogenesis, uncovered novel regulators potentially associated with WAT function, and may provide a new viewpoint for interpretation and treatment of obesity.

最近有报道称，肥胖期间白色脂肪组织（WAT）微环境中发生局部缺氧。脂肪细胞具有独特的生命周期，反映了WAT生态位中脂肪形成的不同阶段。长的非编码RNA（lncRNA）在细胞对缺氧的反应中起重要作用。然而，脂肪形成过程中前脂肪细胞的低氧反应差异性以及lncRNA在该过程中的潜在作用仍有待阐明。在这里，我们评估了脂肪形成过程中主要仓鼠前脂肪细胞的低氧反应，并分析了相同Ribo-Zero RNA-seq库中的mRNA和lncRNA表达。缺氧诱导脂肪形成过程中的HIF-1α蛋白，并引起细胞表型的变化。总共确定了10,318个mRNA在20个文库（五个时间点）中表达，其中3个 在五个时间点（低氧与正常氧）检测到198个差异表达的mRNA（DE mRNA）。功能富集分析揭示了在脂肪形成的不同阶段共有的和特定的缺氧反应途径。缺氧差异调节了与脂肪相关的基因的表达谱，包括脂肪因子，脂肪生成，脂解，增生，肥大，炎症和细胞外基质。我们还鉴定了4296个基本表达的lncRNA，并在五个时间点检测到了1431个DE lncRNA。D0，D1，D3，D7和D11的2个，3个，5个，13个和50个DE mRNA高度相关且位于基因座附近的lncRNA中，主要参与细胞周期，囊泡介导的运输和线粒体组织。ENSCGRT00015041780--希尔普达， TU2105--光盘和 TU17588--Ltbp3。这些lncRNAs可能代表脂肪形成过程中细胞对缺氧的反应中至关重要的调节轴。这项研究剖析了脂肪形成过程中细胞缺氧的影响，发现了可能与WAT功能相关的新型调节剂，并可能为肥胖的解释和治疗提供新的观点。