| Summary: | Phytanic acid and pristanic acid are branched-chain fatty acids, present at micromolar concentrations in the plasma of healthy individuals. Here we show that both phytanic acid and pristanic acid activate the peroxisome proliferator-activated receptor α (PPARα) in a concentration-dependent manner. Activation is observed via the ligand-binding domain of PPARα as well as via a PPAR response element (PPRE). Via the PPRE significant induction is found with both phytanic acid and pristanic acid at concentrations of 3 and 1 μM, respectively. The trans-activation of PPARδ and PPARγ by these two ligands is negligible. Besides PPARα, phytanic acid also trans-activates all three retinoic X receptor subtypes in a concentration-dependent manner. In primary human fibroblasts, deficient in phytanic acid α-oxidation, trans-activation through PPARα by phytanic acid is observed. This clearly demonstrates that phytanic acid itself, and not only its metabolite, pristanic acid, is a true physiological ligand for PPARα. Because induction of PPARα occurs at ligand concentrations comparable to the levels found for phytanic acid and pristanic acid in human plasma, these fatty acids should be seen as naturally occurring ligands for PPARα. These results demonstrate that both pristanic acid and phytanic acid are naturally occurring ligands for PPARα, which are present at physiological concentrations.—Zomer, A. W. M., B. van der Burg, G. A. Jansen, R. J. A. Wanders, B. T. Poll-The, and P. T. van der Saag. Pristanic acid and phytanic acid: naturally occurring ligands for the nuclear receptor peroxisome proliferator-activated receptor α. J. Lipid Res. 2000. 41: 1801–1807.
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