Effects of PPAR gamma agonists on cardiovascular function in obese, non-diabetic patients

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, and when activated by their ligands, they induce perixosome proliferation. Three receptors have been identified: PPAR gamma, PPAR delta, and PPAR alpha, all with different tissue expression. PPAR gamma is predominantly expressed in adipose tissue and regulates the formation of fat cells and their function. The effect of PPAR gamma activation is to enhance the action of insulin in insulin-sensitive tissue by increasing peripheral glucose disposal and decreasing hepatic glucose production. The thiazolidinediones (TZDs) are a class of medications used for treatment and possibly the prevention of type 2 diabetes, which are potent agonists for the PPAR gamma receptor. Because the thiazolidinediones target insulin resistance, these agents may improve many of the risk factors associated with obesity and insulin resistance including dyslipidemia, hypertension, impaired fibrinolysis, and atherosclerosis. The impact of the thiazolidinediones on cardiovascular mortality is currently unclear but it appears that the thiazolidinediones exert numerous non-glycemic effects that may improve cardiovascular outcomes. Several non-TZD PPAR gamma agonists and combined PPAR gamma/alpha effect on cardiovascular disease are also being evaluated. These drugs have anti-inflammatory and vascular properties and are currently the subject of numerous studies targeting the primary and secondary prevention of macrovascular disease in patients with diabetes and insulin resistance and might be developed as anti-atherogenic agents on the basis of their actions.