The expression of PPAR-associated genes is modulated through postnatal development of PPAR subtypes in the small intestine

In this study, we found that the mRNA level of peroxisome proliferator-acti vated receptor (PPAR) alpha, but not of PPAR delta, was elevated in the jej unum during the postnatal development of the rat. Moreover, we found that t he expressions of PPAR-dependent genes, such as acyl-CoA oxidase, L-FABP, a nd I-FABP, were also increased during the postnatal development of the smal l intestine. Electrophoretic mobility shift assay revealed that both the PP AR alpha -9-cis-retinoic acid receptor alpha (RXR alpha) heterodimer and th e PPAR delta -RXR alpha heterodimer bound to the peroxisome proliferator re sponse element (PPRE) of acyl-CoA oxidase and L-FABP genes. The binding of the PPAR alpha -RXR alpha heterodimer to the PPREs of the various genes was enhanced by the addition of PPAR alpha, with a concomitant reduction of th e binding of PPAR delta -RXR alpha to the PPREs. Furthermore, the binding a ctivity of PPAR alpha -RXR alpha, but not PPAR delta -RXR alpha, to the PPR Es was enhanced by the addition of a PPAR ligand, WY14,643. The GAL4-PPAR-c himera reporter assay showed that WY14,643 transactivated the reporter gene through action of PPAR alpha, but not through PPAR delta, in Caco-2 cells. Furthermore, oral administration of a PPAR ligand, clofibrate, during 3 co nsecutive days of the weanling period caused a parallel increase in the mRN A levels of these PPAR-dependent genes. These results suggest that acyl-CoA oxidase, L-FABP and the other PPAR-dependent genes in the small intestine may be coordinately modulated during postnatal development by the dispropor tional expression of PPAR alpha over PPAR delta. (C) 2001 Elsevier Science B.V. All rights reserved.