Peroxisome proliferator-activated receptor δ: a multifaceted metabolic player

Purpose of review Therapeutic strategies to alleviate the growing epidemic of insulin-resistant syndromes (obesity and type 2 diabetes) as well as the conferred cardiovascular disease risk remain sparse. The peroxisome proliferator-activated receptor delta (PPAR delta) has emerged as a versatile regulator of lipid homeostasis and inflammatory signaling, making it an attractive therapeutic target for the treatment and prevention of type 2 diabetes and atherosclerosis. Recent findings PPAR delta activation regulates lipid homeostasis and inflammatory signaling in a variety of cell types, conferring protection from metabolic disease and atherosclerosis. Specifically, PPAR delta activation in the liver stimulates glucose utilization and inhibits gluconeogenesis, which improves insulin resistance and hyperglycemia. In macrophages, PPAR delta-specific activation with synthetic agonists inhibits VLDL-induced triglyceride accumulation and inflammation. In mice, PPAR delta agonists halt the progression of atherosclerosis and stabilize existing lesions by promoting an anti-inflammatory milieu within the diseased macrovasculature. In humans, PPAR delta activation improves insulin sensitivity and reduces atherogenic dyslipidemia via a mechanism complementary to statin monotherapy. Summary Recent advances in the understanding of PPAR delta reveal that activation of this receptor represents a multifaceted therapeutic strategy for the prevention and treatment of insulin-resistant syndromes and atherosclerosis.