Long non-coding RNAs (lncRNAs) have gained extensive attentions due to their significant roles in diverse biological process. However, the potential functions of lncRNAs participation in adipocyte differentiation have not been fully explored. Here we identified a long non-coding RNA called lnc-OAD (IncRNA associated with osteoblast and adipocyte differentiation, transcribed from 1700018A04Rik gene), which modulated 3T3-L1 adipocyte differentiation. Lnc-OAD was up-regulated expression during 3T3-L1 differentiation and stable knockdown of lnc-OAD inhibited adipocyte differentiation in 3T3-L1 cells. Further mechanisms study revealed that silencing of Inc-OAD strongly elevated the protein expression of beta-catenin, and then decreased expression of adipocyte master transcription factors PPAR-gamma and C/EBP alpha. The addition of IWR-1 up-regulated the expression of PPAR-gamma and C/EBP alpha and rescued the impairment of adipocyte differentiation caused by lnc-OAD knockdown. Meanwhile, we also found mitotic clonal expansion (MCE) during the early stage of adipocyte differentiation was inhibited in IncOAD-knockdown cells. Taken together, our study reveals a novel function of lnc-OAD in modulating adipogenesis via influencing mitotic clonal expansion and regulating WNT/beta-catenin signaling pathway. (C) 2019 Elsevier Inc. All rights reserved.