Plants contain potentially toxic compounds for animals and animals have developed physiological strategies to detoxify the ingested toxins during evolution. Feeding mice with various plant seeds and grains showed unexpected result that only sesame killed PPARα-null mice but not wild-type mice at all. A detailed analysis of this observation revealed that PPARα is involved in the metabolism of toxic compounds from plants as well as endobiotic substrates by inducing phase I and phase II detoxification enzymes. PPARα plays a vital role in direct or indirect activation of the relevant genes via the complex network among other xenobiotic nuclear receptors. Thus, PPARα plays its wider and more extensive role in energy metabolism from natural food intake to fat storage than previously thought. 1. Introduction Animals feed on plants for nutritional and tasting reasons. Plants and seeds are important energy sources but they also contain unique compounds and a variety of secondary metabolites some of which are potentially toxic to animals [1]. Chlorophyll, for example, is a green pigment essential for conversion of the energy of sunlight into chemical energy but its derivative contains a branched fatty acid, phytanic acid, which is toxic at least for rodents and human. Popular plant toxins include flavonoids, isoflavonoids, and tannins, but there should be much more. Animals have developed physiological strategies to avoid specific plants and to detoxify the ingested toxins. Physiological detoxification can occur in the mouth and the gut rumen with or without a help of microbes and once absorbed toxins must be detoxified in the intestine and liver [2]. Phytanic acid is completely broken down in the liver and a fatty aldehyde dehydrogenase, FALDH encoded by ALDH3A2, plays a key role in the process [3–5] as its defect causes Sj？gren-Larsson syndrome [6, 7]. However, identification of potentially toxic compounds in plants and seeds is incomplete and the mechanisms of detoxification steps have not been well characterized yet because most animal studies to date have been carried out using artificial laboratory diets. Recently, we found that a nuclear receptor peroxisome proliferator-activated receptor α (PPARα) plays a vital role in induction of a detoxification system by using natural plant seeds as diets for mice [8]. An important role of PPARα in lipid catabolism in the liver has been well established [9], but the PPARα-null mouse shows little phenotypic change when fed with normal laboratory diet [10, 11]. We searched its extrahepatic roles and found that PPARα is
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