Peroxisome proliferator-activated receptor δ: a multifaceted metabolic playerBojic, Lazar A.a; Huff, Murray W.bCurrent Opinion in Lipidology: April 2013 - Volume 24 - Issue 2 - p 171–177 doi: 10.1097/MOL.0b013e32835cc949 GENETICS AND MOLECULAR BIOLOGY: Edited by Robert Hegele Abstract Author Information 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 δ (PPARδ) 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 PPARδ activation regulates lipid homeostasis and inflammatory signaling in a variety of cell types, conferring protection from metabolic disease and atherosclerosis. Specifically, PPARδ activation in the liver stimulates glucose utilization and inhibits gluconeogenesis, which improves insulin resistance and hyperglycemia. In macrophages, PPARδ-specific activation with synthetic agonists inhibits VLDL-induced triglyceride accumulation and inflammation. In mice, PPARδ agonists halt the progression of atherosclerosis and stabilize existing lesions by promoting an anti-inflammatory milieu within the diseased macrovasculature. In humans, PPARδ activation improves insulin sensitivity and reduces atherogenic dyslipidemia via a mechanism complementary to statin monotherapy. Summary Recent advances in the understanding of PPARδ reveal that activation of this receptor represents a multifaceted therapeutic strategy for the prevention and treatment of insulin-resistant syndromes and atherosclerosis. aDepartment of Biochemistry bDepartment of Medicine, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada Correspondence to Murray W. Huff, Robarts Research Institute, Room 4222, The University of Western Ontario, 100 Perth Drive, London, ON, Canada, N6. A 5K8. Tel: +1 519 931 5793; fax: +1 519 931 5227; e-mail: firstname.lastname@example.org © 2013 Lippincott Williams & Wilkins, Inc.