DISTURBANCES IN DIETARY-FAT METABOLISM AND THEIR ROLE IN THE DEVELOPMENT OF ATHEROSCLEROSIS

It was suggested that postprandial lipoproteins (PPLp) may play an imp ortant role in atherogenesis. To examine this hypothesis, we studied P PLp metabolism in normolipidemic individuals and hyperlipoproteinemic (HLP) patients on various diets, physical activity programs, and hypol ipidemic drugs as well as in patients with coronary artery disease (CA D). We used the vitamin A-fat loading test, which labels intestinally derived lipoproteins with retinyl palmitate. Type IV HLP patients demo nstrated a severe defect in chylomicron clearance. Type III HLP patien ts showed severely disordered clearance of chylomicron remnants. Compa red to the saturated fatty acid enriched diet, the omega 6 polyunsatur ated acid enriched diet reduced chylomicrons and their remnant levels by 56 % and 38 %, respectively. The diet enriched in omega 3 polyunsat urated acid decreased chylomicrons and their remnant levels by 67 % an d 53 %, respectively. Physical conditioning reduced chylomicron levels by 37 %. Gemfibrozil decreased chylomicron levels in type IV HLP pati ents. Cholestyramine increased chylomicron levels by 88 %. Bezafibrate reduced chylomicrons and their remnants levels and increased fasting HDL-C in patients with isolated low HDL-C levels. Continuous prolonged intravenous heparin administration inhibited chylomicron clearance. N ormolipidemic patients with CAD had significantly higher plasma levels of chylomicron remnants than matched controls with normal coronary ar teries. The studies reported here demonstrate that both chylomicrons a nd their remnants are present in the plasma of normolipidemic people a nd more so for hyper-or dyslipidemic patients for a prolonged period o f time after fat ingestion. The duration and magnitude of this postpra ndial lipemia can be regulated or altered by such interventions as die t, physical activity, and drugs. Our case control studies strongly sup port the hypothesis that PPLp may play a crucial part in atherogenesis , and therefore justify measuring their levels in high risk patients. We believe that in selected patient groups the use of one or more of t he interventions mentioned here is warranted.