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 (R-AR) and triiodothyronine (TR) receptors i n rat liver. The authors have suggested that PPAR activation may be respons ible for these modifications in nuclear receptor expression. With the aim o f gaining further insight into a possible relationship between the patterns of expression of these receptors, we have examined, using a pharmacologica l model, the effect of a strong and specific PPAR activation induced by bez afibrate, a peroxisome proliferator agent. Activation of PPAR was evaluated by quantifying PPAR alpha mRNA and acyl-CoA oxidase mRNA. The expression o f RAR and TR was determined by assaying the binding properties of these nuc lear receptors and by quantifying the mRNA level of RAR beta and TRalpha1,( beta1) isoforms. After a 10 day treatment of young rats, induction of PPAR (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 (Maxima l Binding Capacity was decreased by 21 and 26%, respectively [P<0.05]) in t he liver was observed. RXR<alpha> mRNA expression was unchanged by treatmen t. Cross-talk between RAR, TR and PPAR signalling path-ways may be implicat ed in the new patterns of nuclear receptor expression observed. The decreas ed expression of RAR and TR reported here could provide a novel element for the understanding of the link between PPAR and tumorigenesis in rat liver.