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  • Title: Genomic and non-genomic interactions of PPARalpha with xenobiotic-metabolizing enzymes.
    Author: Barbier O, Fontaine C, Fruchart JC, Staels B.
    Journal: Trends Endocrinol Metab; 2004 Sep; 15(7):324-30. PubMed ID: 15350604.
    Abstract:
    The hypolipidemic properties of fibrates, synthetic activators of the nuclear receptor, peroxisome proliferator-activated receptor alpha (PPARalpha), have been studied extensively. Recent observations indicate, however, that PPARalpha also functions as a regulator of endobiotic and xenobiotic metabolism in rodents and humans. Activators of PPARalpha affect xenobiotic-metabolizing enzymes (XMEs) at different levels. At the genomic level, the expression of numerous cytochrome P450 (CYP) and phase II conjugating genes is altered in a species-distinct manner on treatment with PPARalpha activators. As a result of such regulatory processes, PPARalpha affects the homeostasis of both its own natural ligands and other compounds including bile acids. At the non-genomic level, PPARalpha activators can act as competitive inhibitors for inactivating other molecules, leading to drug-drug interactions. These global effects of PPARalpha activators on the activity of XMEs are of physiological and pharmaceutical importance, and demonstrate that thorough studies of the actions on XMEs of each novel PPARalpha agonist are warranted.
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