Long noncoding RNA Plnc1 controls adipocyte differentiation by regulating peroxisome proliferator‐activated receptor γ

ABSTRACT Detailed understanding of molecular mechanisms controlling adipogenesis is of great importance to identify new targets for treating obesity. Emerging evidence suggests that long noncoding RNAs (lncRNAs) may play a pivotal role in adipogenesis. Here, we have identified a novel lncRNA, Plnc1, which is transcribed from a position ~25,000 bp upstream of the peroxisome proliferator‐activated receptor γ2(PPAR‐γ2) gene. Plnc1 is abundantly expressed in adipose tissue, and obese mice have higher Plnc1 expression in adipose tissue than nonobese mice. Plnc1 was induced in established adipogenic lines ST2, 3T3‐L1, and C3H10T1/2 as well as in bone marrow stromal cells (BMSCs) after adipogenic treatment. Plnc1 knockdown blocked differentiation of ST2 cells and BMSCs into mature adipocytes, along with the reduction of PPAR‐γ, CCAAT/enhancer binding protein‐α, and adipocyte protein 2. Conversely, overexpression of Plnc1 promoted ST2 cells and BMSCs to fully differentiate. Mechanism studies revealed that Plnc1 could reduce the methylation level of CpG region in the PPAR‐γ2 promoter and enhance the transcriptional activity of the promoter and thereby increase PPAR‐γ2 transcription. Our study suggests that Plnc1 promotes adipogenic differentiation through controlling the key adipogenic transcription factor PPAR‐g and highlights the potential of Plnc1 as a target for new therapies to control metabolic disorders like obesity.—Zhu, E., Zhang, J., Li, Y., Yuan, H., Zhou, J., Wang, B. Long noncoding RNA Plnc1 controls adipocyte differentiation by regulating peroxisome proliferator‐activated receptor γ. FASEB J. 33, 2396–2408 (2019). www.fasebj.org