PPARA
Description
The PPARA (peroxisome proliferator activated receptor alpha) is a protein-coding gene located on chromosome 22.
PPAR-alpha, also known as NR1C1 (nuclear receptor subfamily 1, group C, member 1), is a nuclear receptor protein that functions as a transcription factor and is encoded by the PPARA gene in humans. It belongs to the subfamily of peroxisome proliferator-activated receptors, along with PPAR-delta and PPAR-gamma. PPAR-alpha was first cloned in 1990 by Stephen Green and identified as the nuclear receptor for a diverse class of rodent hepatocarcinogens that cause proliferation of peroxisomes.
PPAR-alpha is primarily activated through ligand binding. 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-hydroxyeicosatetraenoic acid family of arachidonic acid metabolites (e.g., 15(S)-HETE, 15(R)-HETE, and 15(S)-HpETE) and 13-hydroxyoctadecadienoic acid, a linoleic acid metabolite. Synthetic ligands include 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.
PPAR-alpha is a transcription factor regulated by free fatty acids and is 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 acid binding and activation, and peroxisomal and mitochondrial fatty acid β-oxidation.
PPAR-alpha is a ligand-activated transcription factor that plays a crucial role in regulating lipid metabolism. It is activated by endogenous ligands such as 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC) and oleylethanolamide, a naturally occurring lipid that controls satiety. PPAR-alpha serves as a receptor for peroxisome proliferators, including hypolipidemic drugs and fatty acids. It regulates the peroxisomal beta-oxidation pathway of fatty acids and acts as a transcription activator for the ACOX1 and P450 genes. Its transactivation activity requires heterodimerization with RXRA and is inhibited by NR2C2. PPAR-alpha might be involved in transmitting clock information to metabolic pathways regulated by PER2.
PPARA is also known as NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR.
