Peroxisome proliferator-activated receptor (PPAR) (PPAR)

Peroxisome proliferator-activated receptors (PPARs) are a group of three nuclear receptor isoforms—alpha, delta (beta), and gamma—that function as ligand-activated transcription factors [1]. They play central roles in the regulation of energy homeostasis, including lipid and glucose metabolism, as well as cellular differentiation and inflammatory responses [2]. Upon activation by fatty acids or synthetic ligands, PPARs heterodimerize with the retinoid X receptor (RXR) and bind to specific DNA sequences known as peroxisome proliferator response elements (PPREs) to modulate gene expression [3]. PPAR alpha is primarily involved in fatty acid oxidation in the liver, while PPAR gamma is a master regulator of adipogenesis and insulin sensitivity [4]. PPAR delta/beta influences fatty acid catabolism in muscle and thermogenesis [5]. Due to their diverse metabolic effects, PPARs are major therapeutic targets for treating dyslipidemia, type 2 diabetes, and increasingly, metabolic-associated steatohepatitis (MASH) [6].

Other names

PPARsPeroxisome proliferator-activated receptorsNR1C familyNuclear receptor subfamily 1 group CPPAR-alpha (NR1C1)PPAR-delta (NR1C2)PPAR-gamma (NR1C3)

PPARs function as ligand-activated transcription factors. Upon binding to endogenous ligands like fatty acids or synthetic agonists, they undergo a conformational change that allows them to heterodimerize with the Retinoid X Receptor (RXR). This complex then binds to specific DNA sequences called Peroxisome Proliferator Response Elements (PPREs) located in the promoter regions of target genes. This binding recruits coactivator proteins and releases corepressors, leading to the transcriptional regulation of genes involved in lipid transport, fatty acid oxidation, adipogenesis, and glucose metabolism [1][3].