مرکز منطقه ای اطلاع رساني علوم و فناوري - The expression of PPAR-associated genes is modulated through postnatal development of PPAR subtypes in the small intestine

Latin Abstract :

In this study, we found that the mRNA level of peroxisome proliferator-activated receptor (PPAR) α, but not of PPARδ, 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 PPARα-9-cis-retinoic acid receptor α (RXRα) heterodimer and the PPARδ-RXRα heterodimer bound to the peroxisome proliferator response element (PPRE) of acyl-CoA oxidase and L-FABP genes. The binding of the PPARα-RXRα heterodimer to the PPREs of the various genes was enhanced by the addition of PPARα, with a concomitant reduction of the binding of PPARδ-RXRα to the PPREs. Furthermore, the binding activity of PPARα-RXRα, but not PPARδ-RXRα, 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 PPARα, but not through PPARδ, 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 PPARα over PPARδ.