Peroxisome proliferator-activated receptors: from transcriptional control to clinical practice.

Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors that control energy homeostasis through genomic actions. Over the past few years significant advances have been made in unravelling the pathways that are modulated by PPARs. Gene targeting experiments in mice and genetic studies in humans have demonstrated a physiological role for these receptors in adipocyte function, glucose homeostasis, and lipid and lipoprotein metabolism. Recent data indicate that PPARs enhance the reverse cholesterol transport pathway by regulating genes that control macrophage cholesterol efflux, cholesterol transport in plasma and bile acid synthesis. Clinical and experimental evidence suggest that PPAR activation decreases the incidence of cardiovascular disease not only by correcting metabolic disorders, but also through direct actions at the level of the vascular wall. Thus, dysregulation of PPAR activity modulates the onset and evolution of metabolic disorders such as dyslipidaemia, obesity and insulin resistance, predisposing to atherosclerosis.