Peroxisome proliferator-activated receptor alpha plays a vital role in inducing a detoxification system against plant compounds with crosstalk with other xenobiotic nuclear receptors.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is thought to play an important role in lipid metabolism in the liver. To clarify the extra-hepatic and/or unknown function of PPARalpha, we previously performed a proteome analysis of the intestinal proteins and identified 17beta-hydroxysteroid dehydrogenase type 11 as a mostly induced protein by a PPARalpha ligand [Motojima, K. (2004) Eur. J. Biochem. 271, 4141-4146]. Because of its supposed wide substrate specificity, we examined the possibility that PPARalpha plays an important role in inducing detoxification systems for some natural foods by feeding mice with various plant seeds and grains. Feeding with sesame but not others often killed PPARalpha knockout mice but not wild-type mice. A microarray analysis of the sesame-induced mRNAs in the intestine revealed that PPARalpha plays a vital role in inducing various xenobiotic metabolizing enzymes in the mouse intestine and liver. A PPARalpha ligand alone could not induce most of these enzymes, suggesting that there is an essential crosstalk among PPARalpha and other xenobiotic nuclear receptors to induce a detoxification system for plant compounds.