Peroxisome Proliferator-Activated Receptors (PPARs) -A Review

PPARs are ligand-activated transcription factors involved in the transcriptional regulation of key metabolic pathways such as lipid metabolism, adipogenesis, and insulin sensitivity. More recent work implicates all 3 PPAR isotypes (α, γ, and δ) in inflammatory and atherosclerotic pathways. Because these nuclear receptors are activated by extracellular signals and control multiple gene targets, PPARs can be seen as nodes that control multiple inputs and outputs involved in energy balance, providing insight into how metabolism and the vasculature may be integrated. The ongoing clinical use of synthetic PPAR agonists, eg, insulin-sensitizing thiazolidinediones (TZDs) and lipid-lowering fibrates, and the evidence that PPAR activation also may limit inflammation and atherosclerosis have only heightened this interest and the pursuit of novel PPAR agonists. Together, these various observations have stimulated intense interest in PPARs as therapeutic targets and led to large-scale cardiovascular end-point trials with PPAR agonists.