Is PPARβ/δ a Retinoid Receptor?

The broad ligand-binding characteristic of PPAR beta/delta has long hampered identification of physiologically-meaningful ligands for the receptor. The observations that the activity of PPAR beta/delta is supported by fatty acid binding protein 5 (FABP5), which directly delivers ligands from the cytosol to the receptor, suggest that bona fide PPAR beta/delta ligands both activate the receptor, and trigger the nuclear translocation of FABP5. Using these criteria, it was recently demonstrated that all-trans-retinoic acid ( RA), the activator of the classical retinoic acid receptor RAR, also serves as a ligand for PPAR beta/delta. Partitioning of RA between its two receptors was found to be regulated by FABP5, which delivers it to PPAR beta/delta, and cellular RA binding protein II (CRABP-II), which targets it to RAR. Consequently, RA activates PPAR beta/delta in cells that display a high FABP5/CRABP-II expression ratio. It remains to be clarified whether compounds other than RA may also serve as endogenous activators for this highly promiscuous protein. Copyright (C) 2007 D. C. Berry and N. Noy. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.