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Peroxisome proliferator-activated receptor alpha
Peroxisome proliferator-activated receptor alpha (PPAR-alpha), also known as NR1C1 (nuclear receptor subfamily 1, group C, member 1), is a nuclear receptor protein that in humans is encoded by the ''PPARA'' gene. Together with Peroxisome proliferator-activated receptor delta and Peroxisome proliferator-activated receptor gamma, PPAR-alpha is part of the subfamily of Peroxisome proliferator-activated receptors. 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.
== Function ==
PPAR-alpha is a transcription factor and a major regulator of lipid metabolism in the liver. PPAR-alpha is activated under conditions of energy deprivation and is necessary for the process of ketogenesis, a key adaptive response to prolonged fasting. Activation of PPAR-alpha promotes uptake, utilization, and catabolism of fatty acids by upregulation of genes involved in fatty acid transport, fatty binding and activation, and peroxisomal and mitochondrial fatty acid β-oxidation. PPAR-alpha is primarily activated through ligand binding. 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. Endogenous ligands include fatty acids such as arachidonic acid as well as other polyunsaturated fatty acids and various fatty acid-derived compounds such as certain members of the 15-Hydroxyicosatetraenoic acid family of arachidonic acid metabolites, e.g. 15(''S'')-HETE, 15(R)-HETE, and 15(S)-HpETE〔Bio. Cell. 77:67-76, 1993〕〔Mol. Pharmacol. 77:171-184, 2010〕 and 13-Hydroxyoctadecadienoic acid, a linoleic acid metabolite.〔Am J Physiol Gastrointest Liver Physiol. 2014 Sep 15;307(6):G664-71. doi: 10.1152/ajpgi.00064.2014〕
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