Peroxisome proliferator-activated receptor delta (PPAR-delta) (PPARδ)

Peroxisome proliferator-activated receptor delta (PPARδ), also known as PPARβ, is a ligand-activated transcription factor and a member of the nuclear hormone receptor superfamily (UniProt: P35396). It is ubiquitously expressed and serves as a master regulator of lipid and glucose metabolism, particularly by enhancing fatty acid oxidation and mitochondrial biogenesis in skeletal muscle and adipose tissue (PubMed: 11590494). By promoting the switch from glucose to lipid utilization, PPARδ activation improves insulin sensitivity and reduces adiposity, making it a significant therapeutic target for metabolic syndrome and type 2 diabetes (PubMed: 12649486). Beyond metabolism, the receptor modulates inflammatory pathways and plays a role in skin physiology, including wound healing and keratinocyte differentiation (PubMed: 11113131). Pharmacological targeting of PPARδ has led to the development of selective agonists like seladelpar and elafibranor, which are currently investigated for cholestatic liver diseases and metabolic dysfunction-associated steatohepatitis (ClinicalTrials.gov). However, the clinical development of early candidates was historically hindered by concerns regarding potential tumor promotion observed in preclinical rodent models (PubMed: 23661695).

Other names

PPAR-betaNR1C2Nuclear receptor subfamily 1 group C member 2NUCIFAAR

Ligand binding induces a conformational change that facilitates heterodimerization with the Retinoid X Receptor (RXR). This complex binds to Peroxisome Proliferator Response Elements (PPREs) in the promoter regions of target genes, recruiting co-activators to stimulate the transcription of genes involved in fatty acid transport, oxidation, and thermogenesis.