PPAR control of metabolism and cardiovascular functions

Novel peroxisome proliferator-activated receptor (PPAR) agonists are providing new opportunities in the management of metabolic and cardiovascular diseases. In this Review, Staels and colleagues discuss the physiological regulation and actions of the PPAR family and their modulation of the atherogenic lipid profile, atherosclerosis and cardiac remodelling. Peroxisome proliferator-activated receptor-alpha (PPAR alpha), PPAR delta and PPAR gamma are transcription factors that regulate gene expression following ligand activation. PPAR alpha increases cellular fatty acid uptake, esterification and trafficking, and regulates lipoprotein metabolism genes. PPAR delta stimulates lipid and glucose utilization by increasing mitochondrial function and fatty acid desaturation pathways. By contrast, PPAR gamma promotes fatty acid uptake, triglyceride formation and storage in lipid droplets, thereby increasing insulin sensitivity and glucose metabolism. PPARs also exert antiatherogenic and anti-inflammatory effects on the vascular wall and immune cells. Clinically, PPAR gamma activation by glitazones and PPAR alpha activation by fibrates reduce insulin resistance and dyslipidaemia, respectively. PPARs are also physiological master switches in the heart, steering cardiac energy metabolism in cardiomyocytes, thereby affecting pathological heart failure and diabetic cardiomyopathy. Novel PPAR agonists in clinical development are providing new opportunities in the management of metabolic and cardiovascular diseases.

Automated summary

Novel PPAR agonists offer new opportunities for managing metabolic and cardiovascular diseases by regulating gene expression, lipid metabolism, insulin sensitivity, glucose metabolism, and cardiovascular health. Activation of PPARs by specific ligands can have antiatherogenic, anti-inflammatory, and metabolic benefits, making them important therapeutic targets in the treatment of various diseases.