Peroxisome proliferator-activated receptor (PPAR) alpha activation and itsconsequences in humans

Amphipathic carboxylates collectively defined as peroxisome proliferators ( PP) induce in rodents a pleiotropic effect, mediated by the peroxisome prol iferator-activated receptor alpha (PPAR alpha). Treatment with PP results i n rodents in hypolipidemia, peroxisome proliferation and liver hypertrophy and hyperplasia leading to non-genotoxic hepatocarcinogenesis. In contrast to rodents, the hypolipidemic effect exerted by PP in humans is not accompa nied by peroxisome proliferation nor by induction of peroxisomal beta-oxida tion or other activities induced by PP in rodents. Non-responsiveness in hu mans may be ascribed to a missing liver component in the PPAR alpha transdu ction pathway specifically involved with transcriptional modulation of chro mosomal PPAR alpha responsive genes. Hence, biological effects exerted by P P in the human liver are likely to be mediated by a transduction pathway in dependent of PPAR alpha. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.