Depletion of Jmjd1c impairs adipogenesis in murine 3T3-L1 cells

Differentiation of adipocytes is a highly regulated process modulated by multiple transcriptional co-activators and co-repressors. JMJD1C belongs to the family of jumonji C (jmjC) domain-containing histone demethylases and was originally described as a ligand-dependent co-activator of thyroid hormone and androgen receptors. Here, we explored the potential role of Jmjdlc in white adipocyte differentiation. To investigate the relevance of Jmjdlc in adipogenesis, murine 3T3-L1 preadipocyte cells with transient knock-down of Jmjdlc (3T3_Jmjdlc) were generated. Depletion of Jmjdlc led to the formation of smaller lipid droplets, reduced accumulation of triglycerides and maintenance of a more fibroblast-like morphology after adipocyte differentiation. Concomitantly, insulin stimulated uptake of glucose and fatty acids was significantly reduced in 3T3_Jmjdlc adipocytes. In line with these observations we detected lower expression of key genes associated with lipid droplet formation (Plinl, Plin4, Cidea) and uptake of glucose and fatty acids (Glut4, Fatpl, Fatp4, Aqp7) respectively. Finally, we demonstrate that depletion of Jmjdlc interferes with mitotic clonal expansion (MCE), increases levels of H3K9me2 (dimethylation of lysine 9 of histone H3) at promotor regions of adipogenic transcription factors (C/EBPs and PPARy) and leads to reduced induction of these key regulators. In conclusion, we have identified Jmjdlc as a modulator of adipogenesis. Our data suggest that Jmjdlc may participate in MCE and the activation of the adipogenic transcription program during the induction phase of adipocyte differentiation in 3T3-L1 cells.