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

Peroxisome proliferator-activated receptor delta (PPAR-δ), also known as PPAR-β, is a ligand-activated transcription factor and a member of the nuclear receptor superfamily [UniProt P35396]. It is ubiquitously expressed but found at high levels in tissues with high fatty acid oxidation rates, such as skeletal muscle, heart, and liver [NCBI Gene 5467]. PPAR-δ functions by forming a heterodimer with the retinoid X receptor (RXR) and binding to specific DNA sequences called peroxisome proliferator response elements (PPREs) to regulate the expression of genes involved in lipid metabolism, glucose uptake, and energy expenditure [Journal of Lipid Research, 2016]. In disease contexts, PPAR-δ is a major therapeutic target for metabolic disorders, including dyslipidemia, obesity, and type 2 diabetes, due to its ability to improve insulin sensitivity and lower circulating lipids [Journal of Lipid Research, 2016]. Additionally, it has emerged as a target for chronic liver diseases like primary biliary cholangitis (PBC) and non-alcoholic steatohepatitis (NASH) because of its anti-inflammatory and anti-fibrotic properties [NEJM, 2024]. Despite its therapeutic potential, drug development has faced challenges due to concerns over potential tumor-promoting effects observed in long-term animal studies with certain early agonists [Nature Reviews Cancer, 2012].

Other names

Peroxisome proliferator-activated receptor betaPPAR-betaPPARDNR1C2Nuclear receptor subfamily 1 group C member 2NUC1

Agonism of the receptor leads to heterodimerization with the Retinoid X Receptor (RXR), which then binds to Peroxisome Proliferator Response Elements (PPRE) in the promoter regions of target genes to modulate transcription [UniProt P35396, Journal of Lipid Research, 2016].