ABSTRACT: Local hypoxia is recently reported to be occur in white adipose tissue (WAT) microenvironment at obesity. Adipocyte have own life cycle that reflect in different stages of adipogenesis in WAT niche. Long noncoding RNAs (lncRNAs) play an important role in cellular response to hypoxia. However, the different hypoxic responses of preadipocytes during adipogenesis and the potential role of lncRNAs in this process remain to be elucidated. Here we evaluated the different hypoxic responses of primary hamster preadipocytes during adipogenesis and analyzed the expression of mRNAs and lncRNAs from same Ribo-Zero RNA-seq libraries. Hypoxia induced HIF-1α protein during adipogenesis and caused the divergent changes of cell phenotypes. A total of 10,318 mRNAs were identified to be expressed in twenty libraries (five timepoints), and 149, 326, 365, 1099, 2504 differentially expressed mRNAs (DE mRNAs) were detected in D0, D1, D3, D7 and D11, respectively (hypoxia vs normoxia). Functional enrichment analysis revealed the shared and specific hypoxia response pathways in different stages of adipogenesis. Hypoxia differentially modulates the expression profile of adipose-associated genes, including adipokines, lipogenesis, lipolysis, hyperplasia, hypertrophy, inflammatory and extracellular matrix (ECM). We also identified 4,296 lncRNAs that were substantially expressed and detected 1,431 DE lncRNAs in five timepoints. Afterward, 2, 3, 5, 13 and 50 DE mRNAs in D0, D1, D3, D7 and D11, respectively, were highly correlated and loci-nearby with DE lncRNAs, and were mainly involved in cell cycle, vesicle-mediated transport and mitochondrion organization. We also identified twenty-eight one-to-one lncRNA-mRNA pairs that might be closely related to adipocyte function, such as ENSCGRT00015041780-Hilpda, TU2105-Cdsn, TU17588-Ltbp3. These lncRNAs may represent the crucial regulation axis in cellular response to hypoxia during adipogenesis. Altogether, this study dissected the effects of hypoxia in the cell during adipogenesis, and uncovered novel regulator potentially associated with obesity and may provide a new view for interpretation and treatment of obesity.
