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

Peroxisome proliferator-activated receptor delta (PPARδ), also known as PPARβ, is a ligand-activated transcription factor belonging to the nuclear receptor superfamily (UniProt: P16671). It is ubiquitously expressed but found at high levels in tissues with high fatty acid oxidation rates, such as skeletal muscle, heart, and adipose tissue (PubMed: 26073486). PPARδ plays a critical role in regulating lipid metabolism, glucose homeostasis, and energy expenditure by promoting the expression of genes involved in fatty acid uptake and beta-oxidation (NCBI Gene: 5467). Beyond metabolism, it exerts anti-inflammatory effects and is involved in wound healing and cell differentiation (PubMed: 12665521). In clinical medicine, PPARδ is a major therapeutic target for metabolic and hepatic diseases, including dyslipidemia, nonalcoholic steatohepatitis (NASH), and primary biliary cholangitis (PBC) (PubMed: 31513942). Drugs targeting this receptor, such as seladelpar and elafibranor, act as agonists to improve lipid profiles and reduce hepatic inflammation and fibrosis (ClinicalTrials.gov: NCT03602560). However, concerns regarding potential pro-carcinogenic effects observed in preclinical rodent models have historically complicated its drug development path (PubMed: 23536517).

Other names

Peroxisome proliferator-activated receptor betaPPAR-deltaPPAR-betaNR1C2Nuclear receptor subfamily 1 group C member 2NUC1

Agonism; the receptor forms a heterodimer with the Retinoid X Receptor (RXR) upon ligand binding, which then binds to Peroxisome Proliferator Response Elements (PPREs) in the promoter regions of target genes to modulate their transcription.