FENOFIBRATE IMPROVES POSTPRANDIAL CHYLOMICRON CLEARANCE IN IIB-HYPERLIPOPROTEINEMIA

In 11 patients with IIB hyperlipoproteinemia we studied fasting lipids , lipoproteins, lipoprotein-modifying enzymes, and postprandial lipid metabolism after a standardized oral fat load supplemented with vitami n A before and 12 weeks after treatment with fenofibrate, a third-gene ration fibric acid derivative. Fasting plasma cholesterol, triglycerid es, low-density lipoprotein cholesterol decreased significantly (P < 0 .05, P < 0.01, P < 0.01), high-density lipoprotein subfraction 3 chole sterol increased significantly (P < 0.05), and high-density lipoprotei n subfraction 2 cholesterol remained unchanged. Postprandial lipemia, i.e., the integrated postprandial triglyceride concentrations correcte d for the fasting triglyceride level, and postprandial chylomicron con centrations, as assessed by biosynthetic labeling of chylomicrons with retinyl palmitate, decreased by 40.6% and 60.1% (P < 0.05; P < 0.05), respectively. The activity of lipoprotein lipase (LPL) increased by 3 3.6% (P < 0.05); the increase in LPL during fenofibrate treatment was positively correlated with the increase in high-density lipoprotein ch olesterol (r = 0.84; P < 0.005). Hepatic lipase and cholesteryl ester transfer protein mass and activity remained unchanged. We conclude tha t lipid-lowering therapy with fenofibrate ameliorates fasting and, mor e profoundly, postprandial lipoprotein transport in hypertriglyceridem ia by curbing postprandial triglyceride and chylomicron accumulation, at least in part, through an increase in LPL activity.