A simple method to screen ligands of peroxisome proliferator-activated receptor δ

Abstract Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the nuclear receptor superfamily directly modulating gene expression by binding to specific ligands. Recently, it has been reported that PPARδ ligands play an essential role in improvement of metabolic disorders and skin disorders. We introduce an enzyme-linked immunosorbent assay (ELISA) to screen new PPARδ ligands. This method is based on the activation mechanism of PPARδ where the ligand binding to PPARδ induces the interaction of the receptor with transcriptional co-activators. We optimized a simple ELISA method for screening PPARδ ligands. Among co-activators such as SRC-1, TIF-2, and p300, PPARδ had more strong binding with SRC-1 in an ELISA system. GW501516 and linoleic acid, the well-known ligands of PPARδ, increased the binding between PPARδ and co-activators in a ligand dose-dependent manner. The recruitment of co-activator SRC-1 was also more effective than those of TIF-2 and p300. We optimized and developed a novel and useful ELISA system for the mass screening of PPARδ ligands. This screening system may be useful in the development of drugs for metabolic disorders and skin disorders.