PPARα as a Transcriptional Regulator for Detoxification of Plant Diet-Derived Unfavorable Compounds

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

Identification of a Gene Sharing a Promoter and Peroxisome Proliferator-Response Elements With Acyl-CoA Oxidase Gene

Many mammalian genes are clustered on the genomes, and hence the genes in the same cluster can be regulated through a common regulatory element. We indeed showed previously that the perilipin/PEX11α gene pair is transactivated tissue-selectively by PPARγ and PPARα, respectively, through a common binding site. In the present study, we identified a gene, named GSPA, neighboring a canonical PPAR target, acyl-CoA oxidase (AOX) gene. GSPA expression was induced by a peroxisome proliferator, Wy14,643, in the liver of wild-type mice, but not PPARα-null mice. GSPA and AOX share the promoter and two peroxisome proliferator-response elements. GSPA mRNA was also found in the heart and skeletal muscle, as well as 3T3-L1 cells. GSPA encodes a protein of 161 amino acids that is enriched in 3T3-L1 cells. Even other gene pairs might be regulated through common sequence elements, and conversely it would be interesting how each gene is aptly regulated in clusters