Ppars: Nuclear Receptors for Fatty Acids Eicosanoids, and Xenobiotics

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Abstract
The induction of gene expression in response to hormones and nutrient-derived signaling molecules is important not only for tissue remodeling and cellular differentiation during development, but also for various aspects of homeostasis during adulthood, One mechanism by which cells respond to signaling molecules involves a family of nuclear receptors that activate transcription in a ligand-dependent manner. The peroxisome proliferator-activated receptors (PPARs) are a class of these transcription factors1 for review. We have previously identified PPARα as a nuclear receptor for the eicosanoid LTB4 and also for xenobiotics2,3 such as the lipid-lowering drug Wy 14,643 and the arachidonic acid analogue ETYA. These studies also link, in vivo, PPARα function with inflammation control. Here, we describe an assay for evaluating various compounds as ligands for the three PPAR isotypes. These results reveal that PPARs are nuclear receptors for 8S-HETE and polyunsaturated fatty acids, and also highlight the differences in ligand specificity between the different PPAR isotypes.