PPARs, metabolic disease and atherosclerosis

PPAR-alpha belongs to the family of nuclear receptors. Activated PPAR-alpha stimulates the expression of genes involved in fatty acid and lipoprotein metabolism. PPAR-alpha activators, such as the normolipidaemic fibric acids, decrease triglyceride concentrations by increasing the Zn expression of lipoprotein lipase and decreasing apo C-III concentration. Furthermore, they increase HDL-cholesterol by increasing the expression of apo A-I and apo A-II. PPAR-alpha activation by fibric acids improves insulin sensibility, and decreases thrombosis and vascular inflammation, PPAR-alpha activators (gemfibrozil) decrease the risk of coronary heart disease in patients with normal LDL-cholesterol and low HDL-cholesterol (VA-HIT) and they slow the progression of premature coronary atherosclerosis (BECAIT) (bezafibrate), particularly in patients with type 2 diabetes (DAIS) (fenofibrate). (C) 2001 Academic Press.