Hypolipidemia induced by PPARalpha agonists: HNF-4alpha as an alternative to PPARalpha.

This critical review examines the putative role played by peroxisome proliferator-activated receptor alpha (PPARalpha) in the hypolipidemic activity induced by peroxisome proliferators/PPARalpha agonists. The hypolipidemic effect of peroxisome proliferators mediated in rodents by hepatic PPARalpha activation is independent of PPARalpha in humans, and is transduced by direct suppression of hepatocyte nuclear factor-4alpha by the CoA-thioesters of hypolipidemic peroxisome proliferators. A novel target for hypolipidemic drugs in humans and an updated risk assessment for human hypolipidemic drugs are implied.