Peroxisome proliferator-activated receptor alpha (PPARα) (PPARα)

Peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily that serves as a master regulator of lipid metabolism [1, 2]. It is highly expressed in tissues with high oxidative rates, such as the liver, heart, and skeletal muscle, where it promotes the uptake, utilization, and catabolism of fatty acids through the upregulation of genes involved in mitochondrial and peroxisomal beta-oxidation [2, 13]. Upon activation by endogenous ligands like free fatty acids or synthetic ligands such as fibrates, PPARα heterodimerizes with the retinoid X receptor (RXR) to bind specific DNA sequences known as peroxisome proliferator response elements (PPREs) [1, 9]. Clinically, PPARα is a primary therapeutic target for treating dyslipidemia and hypertriglyceridemia, as its activation effectively lowers plasma triglycerides and increases high-density lipoprotein (HDL) cholesterol [2, 8]. Beyond its metabolic roles, PPARα exerts significant anti-inflammatory effects by antagonizing pro-inflammatory signaling pathways like NF-κB, making it a target of interest for cardiovascular diseases and metabolic-associated steatotic liver disease (MASLD) [3, 9]. Recent research also explores PPARα inhibition as a strategy in oncology to disrupt the fatty acid oxidation that fuels certain tumor types [7].

Other names

PPARANR1C1Nuclear receptor subfamily 1 group C member 1PPAR-alphaPPARα pathway

Agonism: PPARα forms a heterodimer with the Retinoid X Receptor (RXR), binds to Peroxisome Proliferator Response Elements (PPREs), and recruits co-activators to induce transcription of genes involved in fatty acid oxidation and lipid transport [1, 9]. Inhibition: Small molecules block PPARα-mediated transcription to reduce fatty acid oxidation in tumor cells [7].