An oral fat tolerance test was administered to groups of normal male and female volunteers, and to a group of patients undergoing coronary angiography. The changes in plasma lipoprotein fractions were monitored during the post prandial phase. Vitamin A (retinyl palmitate) was added to the fat load to mark lipoproteins of intestinal derivation. In healthy male subjects the post prandial rise in plasma triglyceride was associated with an increase in the size of lipoproteins of density less than 1.006kg/l, and with characteristic changes in the composition of the other lipoprotein classes. Triglyceride rose in LDL and HDL in parallel with the rise in p<1.006 triglyceride. Phospholipid in LDL and HDL continued to rise beyond the peak of triglyceridaemia. HDL cholesteryl esters fell at the peak, and the free cholesterol content of LDL and HDL rose in the late phase of lipaemia. Retinyl palmitate was present in significant amounts 24 hours after the initial fat meal. The pattern of changes was interpreted in terms of lipoprotein surface and core lipid compositions. There was a decline in the ratio of free cholesterol to phospholipid in the surface regions of LDL, and a fall in the ratio of cholesteryl ester to triglyceride in the core of both LDL and HDL. Post prandial triglyceridaemia correlated positively with fasting levels of the apoB containing lipoproteins, and negatively with HDL. There was an inverse correlation with post heparin lipoprotein and hepatic lipase activities. Triglyceridaemia was positively related to the actual free cholesterol content of LDL, but negatively to the post prandial changes in LDL free cholesterol. The fall in HDL cholesteryl ester and cholesteryl ester/triglyceride ratio were negatively related to triglyceridaemia. Females had lower fasting VLDL and higher HDL than males. Post prandial triglycerides were less and post heparin lipoprotein lipase activity was greater. There was a greater increase in plasma free cholesterol during lipaemia and a fall as opposed to a rise in plasma cholesteryl ester. Retinyl palmitate levels were less at all times, but most significantly at 24 hours after the fat meal. In subjects undergoing coronary angiography fasting LDL cholesterol was positively related and HDL cholesterol negatively related to angiogram score. Post prandial triglyceridaemia was positively related to angiogram score, but fasting triglycerides were not. The best single predictor of angiogram score was retinyl palmitate levels 24 hours after the fat load. Retinyl ester levels were also strongly related to LDL cholesterol. Increasing the cholesterol content of the fat load had no effect on post prandial lipids. Decreasing the fatty acid saturation of the test meal decreased triglyceridaemia only slightly. Chylomicrons obtained after saturated or unsaturated fat loads differed in the composition of their triglyceride content, but not in the composition of phospholipid fatty acids. These chylomicrons were catabolised at similar rates during in vitro lipolysis. Three weeks treatment with fenofibrate reduced fasting VLDL and LDL, and increased HDL3. Post prandial triglycerides were decreased, and the post prandial fall in HDL cholesteryl esters was eliminated. Retinyl palmitate was apparently increased during lipaemia but levels were unchanged at 24 hours. Three weeks treatment with nicotinic acid reduced fasting VLDL and LDL and increased HDL2. Post prandial triglycerides were reduced but retinyl esters were unchanged. There were no significant changes in other aspects of post prandial lipid flux. Possible mechanisms explaining these findings are discussed.
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