TNF‐α downregulates the peroxisome proliferator activated receptor‐α and the mRNAs encoding peroxisomal proteins in rat liver

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Abstract
We have studied the effects of TNF‐α on the mRNAs coding for the peroxisome proliferator activated receptor α (PPAR‐α), and for catalase (Cat), acyl‐CoA oxidase (AOX), multifunctional enzyme (PH), and β‐actin in rat liver. Total RNA was isolated from livers of male SD‐rats 16 h after administration of a single dose of 25 μg TNF‐α and mRNAs were analyzed by a novel dot blot RNase protection assay. The mRNAs for PPAR‐α and for Cat, AOX and PH were significantly reduced by TNF‐treatment. In addition, the level of PPAR‐α protein was also decreased after TNF. In contrast, the mRNA for β‐actin was markedly increased implying that the effect of TNF on PPAR‐α and the peroxisomal mRNAs is highly selective. This effect may have important implications in perturbation of the lipid metabolism induced by TNF‐α.