Is PPARbeta/delta a Retinoid Receptor?
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Updated: Jul 7, 2026

Quantitative Analysis of Dietary Vitamin A Metabolites in Murine Ocular and Non-Ocular Tissues Using High-Performance Liquid Chromatography
Published on: December 27, 2024
1Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Abstract:
The broad ligand-binding characteristic of PPARbeta/delta has long hampered identification of physiologically-meaningful ligands for the receptor. The observations that the activity of PPARbeta/delta is supported by fatty acid binding protein 5 (FABP5), which directly delivers ligands from the cytosol to the receptor, suggest that bona fide PPARbeta/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 PPARbeta/delta. Partitioning of RA between its two receptors was found to be regulated by FABP5, which delivers it to PPARbeta/delta, and cellular RA binding protein II (CRABP-II), which targets it to RAR. Consequently, RA activates PPARbeta/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.
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