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Is PPARbeta/delta a Retinoid Receptor?
1Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA.
PPAR Research
|February 16, 2008
Summary
Fatty acid binding protein 5 (FABP5) helps identify ligands for PPARbeta/delta. All-trans-retinoic acid (RA) activates both RAR and PPARbeta/delta, with FABP5 regulating RA
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) exhibits broad ligand-binding, complicating the identification of its physiological ligands.
- Fatty acid binding protein 5 (FABP5) is crucial for PPARbeta/delta activity, delivering ligands from the cytosol to the receptor.
- Identifying bona fide PPARbeta/delta ligands requires them to activate the receptor and induce FABP5 nuclear translocation.
Purpose of the Study:
- To investigate whether all-trans-retinoic acid (RA), a known RAR activator, also functions as a PPARbeta/delta ligand.
- To elucidate the role of FABP5 and cellular retinoic acid binding protein II (CRABP-II) in regulating RA partitioning between RAR and PPARbeta/delta.
- To determine the cellular conditions under which RA activates PPARbeta/delta.
Main Methods:
- Utilized criteria of receptor activation and FABP5 nuclear translocation to identify endogenous PPARbeta/delta ligands.
- Investigated the interaction of RA with PPARbeta/delta and RAR.
- Assessed the influence of FABP5 and CRABP-II expression levels on RA's receptor preference.
Main Results:
- All-trans-retinoic acid (RA) was identified as a ligand for both RAR and PPARbeta/delta.
- FABP5 facilitates RA delivery to PPARbeta/delta, while CRABP-II targets RA to RAR.
- RA activates PPARbeta/delta in cells with a high FABP5/CRABP-II expression ratio.
Conclusions:
- RA acts as a dual ligand for RAR and PPARbeta/delta, with its partitioning regulated by FABP5 and CRABP-II.
- Cellular expression levels of FABP5 and CRABP-II dictate whether RA activates RAR or PPARbeta/delta.
- Further research is needed to identify other potential endogenous activators for the promiscuous PPARbeta/delta receptor.
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