proliferatoractivated

Proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors activated by lipid-related ligands. The name reflects their association with peroxisome proliferation observed in some rodent studies, a clue to their role in lipid metabolism. PPARs belong to the nuclear receptor superfamily and regulate gene expression in response to fatty acids and their metabolites.

There are three main human isoforms: PPAR-α (PPARα), PPAR-β/δ (PPARβ/δ), and PPAR-γ (PPARγ). They form heterodimers with the retinoid X receptor (RXR) and bind to PPAR response elements in the promoters of target genes to modulate transcription. Endogenous ligands include long-chain fatty acids and eicosanoids; synthetic ligands include fibrates (PPARα agonists) and thiazolidinediones (PPARγ agonists). Selective PPAR modulators are an area of ongoing research, with PPARδ agonists studied for effects on energy expenditure and lipid metabolism.

Physiologically, PPARs regulate lipid and glucose metabolism, adipocyte differentiation, inflammation, and energy balance. PPARα promotes fatty acid oxidation in liver and muscle; PPARγ promotes adipogenesis and improves insulin sensitivity in adipose tissue; PPARβ/δ influences fatty acid oxidation and energy management across several tissues. The receptors also intersect with inflammatory pathways and may influence cellular differentiation and growth in various contexts.

Clinically, PPAR-targeting drugs are used to treat dyslipidemia (PPARα agonists) and type 2 diabetes (PPARγ agonists). Investigational agents and dual or pan-PPAR modulators aim to address metabolic syndrome and inflammatory diseases. Adverse effects vary by isoform and compound, with edema and weight gain common for PPARγ ligands and other risks noted for certain agents.