Dlx5 Represses The Transcriptional Activity Of Ppar Gamma

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master transcription factor in adipocyte differentiation, while distal-less homeobox 5 (Dlx5) is essential for initiating osteoblast differentiation by driving Runt-related transcription factor 2 expression. Considering that adipocytes and osteoblasts share common progenitors, there is a reciprocal correlation between bone and fat formation. However, the mechanism by which Dlx5 controls PPAR gamma remains unclear. We elucidated that Dlx5 physically hinds to PPAR gamma during immunoprecipitation; in particular, the ligand-binding and DNA-binding domains of PPAR gamma were involved in the interaction. Transcriptional activity of PPAR gamma was significantly decreased by Dlx5 overexpression, whereas the opposite results were detected with Dlx5 knockdown. Rosiglitazone, a PPAR gamma agonist, further enhanced the PPAR gamma-induced transcriptional activity; however, Dlx5 overexpression effectively repressed the rosiglitazone-mediated increase in activity. Finally, DNA-binding affinity assay revealed that Dlx5 interrupts the interaction of PPAR gamma with the PPAR gamma response element promoter. In conclusion, our findings indicate that Dlx5 impedes PPAR gamma-induced activity, and it may be useful for managing diabetes drugmediated obesity.