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-activated receptor (PPAR) alpha, but not of PPAR delta, was elevated in the jejunum during the postnatal development of the rat. Moreover, we found that the expressions of PPAR-dependent genes, such as acyl-CoA oxidase, L-FABP, and I-FABP, were also increased during the postnatal development of the small intestine. Electrophoretic mobility shift assay revealed that both the PPAR alpha -9-cis-retinoic acid receptor alpha (RXR alpha) heterodimer and the PPAR delta -RXR alpha heterodimer bound to the peroxisome proliferator response 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 the binding of PPAR delta -RXR alpha to the PPREs. Furthermore, the binding activity of PPAR alpha -RXR alpha, but not PPAR delta -RXR alpha, to the PPREs was enhanced by the addition of a PPAR ligand, WY14,643. The GAL4-PPAR-chimera 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 consecutive days of the weanling period caused a parallel increase in the mRNA 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 disproportional expression of PPAR alpha over PPAR delta. (C) 2001 Elsevier Science B.V. All rights reserved.