It was the first member of the PPAR family to be cloned in 1990 by Stephen Green and has been identified as the nuclear receptor for a diverse class of rodent hepatocarcinogens that causes proliferation of peroxisomes.

Synthetic ligands include the fibrate drugs, which are used to treat hyperlipidemia, and a diverse set of insecticides, herbicides, plasticizers, and organic solvents collectively referred to as peroxisome proliferators.

[13] Mice lacking PPAR-alpha also have an impaired response to fasting, characterized by major metabolic perturbations including low plasma levels of ketone bodies, hypoglycemia, and fatty liver.

), which is a Docosanoid derivative of the omega-3 fatty acid DHA was isolated as an endogenous high affinity ligand for PPAR-alpha in the rat and mouse brain.

[18] Both high sugar and low protein diets elevate the circulating liver hormone FGF21 in humans by means of PPAR-α, although this effect can be accompanied by FGF21-resistance.

[19] Amezalpat is an oral, small molecule, selective antagonist of PPAR alpha being developed for treatment of hepatocellular carcinoma by Tempest therapeutics and has already gained orphan drug and fast track designation by the FDA.

PPAR-α has been shown to interact with: This article incorporates text from the United States National Library of Medicine, which is in the public domain.