Peroxisome proliferator-activated receptor (PPAR) alpha activation and its consequences in humans.

Amphipathic carboxylates collectively defined as peroxisome proliferators (PP) induce in rodents a pleiotropic effect, mediated by the peroxisome proliferator-activated receptor alpha (PPAR alpha). Treatment with PP results in 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 accompanied by peroxisome proliferation nor by induction of peroxisomal beta-oxidation or other activities induced by PP in rodents. Non-responsiveness in humans may be ascribed to a missing liver component in the PPAR alpha transduction pathway specifically involved with transcriptional modulation of chromosomal PPAR alpha responsive genes. Hence, biological effects exerted by PP in the human liver are likely to be mediated by a transduction pathway independent of PPAR alpha.