Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver

It has recently been shown that high-fat diets induce the expression of per oxisome proliferator-activated receptor (PPAR) with a concomitant decrease in expression of retinoic acid (RAR) and triiodothyronine (TR) receptors in rat liver. The authors have suggested that PPAR activation may be responsi ble for these modifications in nuclear receptor expression. With the aim of gaining further insight into a possible relationship between the patterns of expression of these receptors, we have examined, using a pharmacological model, the effect of a strong and specific PPAR activation induced by beza fibrate, a peroxisome proliferator agent. Activation of PPAR was evaluated by quantifying PPAR alpha mRNA and acyl-CoA oxidase mRNA. The expression of RAR and TR was determined by assaying the binding properties of these nucl ear receptors and by quantifying the mRNA level of RAR beta and TR alpha (1 ),beta (1) isoforms. After a 10 day treatment of young rats, induction of P PAR (PPAR alpha mRNA was increased by 40% [P<0.05 and acyl-CoA oxidase mRNA by 411% [P<0.001]) and a concomitant decrease of RAR and TR expression (Ma ximal Binding Capacity was decreased by 21 and 26%, respectively [P<0.05]) in the liver was observed. RXR<alpha> mRNA expression was unchanged by trea tment. Cross-talk between RAR, TR and PPAR signalling pathways may be impli cated in the new atp terns of nuclear receptor expression observed. The dec reased expression of RAR and TR reported here could provide a novel element for the understanding of the link between PPAR and tumorigenesis in rat li ver.