Peroxisome proliferator-activated receptor alpha, delta, gamma (PPARα, PPARδ, PPARγ)

Peroxisome proliferator-activated receptors alpha, delta, and gamma (PPARα, PPARδ, and PPARγ) are closely related members of the nuclear hormone receptor superfamily, functioning as ligand-activated transcription factors that regulate genes involved in lipid and glucose metabolism, energy balance, and inflammation. Each receptor is encoded by a distinct gene and features a domain structure typical of nuclear receptors, including an N-terminal activation domain, a central DNA-binding domain with zinc fingers, a hinge region, and a C-terminal ligand-binding domain. - PPARα is most highly expressed in the liver, heart, and brown fat, playing key roles in fatty acid oxidation and energy mobilization, especially during fasting. - PPARδ (also PPARβ) is broadly expressed and central to lipid metabolism, energy homeostasis, and anti-inflammatory effects. - PPARγ is mainly expressed in adipose tissue and is a master regulator of adipogenesis, insulin sensitization, and fatty acid storage. These receptors are targets for drugs treating metabolic diseases such as diabetes and dyslipidemia, and are being investigated for roles across a wide array of diseases including cardiovascular and inflammatory conditions. Pharmacologic modulation occurs via small-molecule ligands (endogenous and synthetic) that influence receptor conformation and DNA binding, altering expression of key metabolic genes

Other names

NR1C1Nuclear receptor subfamily 1 group C member 1PPARβNR1C2Nuclear receptor subfamily 1 group C member 2NR1C3Glitazone reverse insulin resistance receptor

Ligand binding induces conformational changes, leading to heterodimerization with retinoid X receptor (RXR), binding to peroxisome proliferator response elements (PPREs) in DNA, and modulation (activation/repressions) of target gene transcription Drugs can act as full agonists, partial agonists, antagonists, or inverse agonists