PPAR

PPAR stands for peroxisome proliferator-activated receptor, a subfamily of nuclear hormone receptors that regulate gene expression in response to lipid-derived ligands. PPARs form heterodimers with retinoid X receptor (RXR) and bind to PPAR response elements in the promoters of target genes to regulate transcription. They are activated by fatty acids and eicosanoids, and function through coactivator and corepressor proteins to modulate chromatin structure and transcription.

There are three main isoforms: PPAR-alpha (PPAR-α), PPAR-beta/delta (PPAR-β/δ), and PPAR-gamma (PPAR-γ). PPAR-α is highly expressed in liver, heart, and muscle and promotes fatty acid oxidation and lipoprotein metabolism. PPAR-β/δ is ubiquitously expressed and influences fatty acid oxidation and energy expenditure, particularly in muscle. PPAR-γ is most abundant in adipose tissue and drives adipogenesis and insulin sensitivity, also modulating inflammatory responses.

Physiologically, PPARs coordinate lipid and glucose metabolism, energy balance, and inflammation. They regulate genes involved in fatty acid transport, beta-oxidation, lipoprotein metabolism, adipokine production, and insulin signaling. PPAR activity affects lipid homeostasis, glucose tolerance, and inflammatory processes in various tissues.

Clinically, PPARs are targets for metabolic disease drugs. PPAR-α agonists (fibrates) lower triglycerides and modestly raise HDL. PPAR-γ agonists (thiazolidinediones) improve insulin sensitivity in type 2 diabetes but carry risks such as weight gain and edema. Dual or pan-PPAR agonists have been developed to exploit complementary actions, though safety and efficacy vary.

Research continues on selective PPAR modulators to maximize beneficial effects while reducing adverse outcomes. Species differences and context-dependent effects complicate interpretation of animal studies.