Fatty Add Concentration In Serum Chytomlcron Fractions After Ingestion of Oil Containing Low , Medium , or High Quantities of Oxidized Upld Fatty Add Low Medium High

We examined whether oxidized lipids in the diet determine the levels of oxidized lipid in human postprandial serum chylomicrons. After we fed subjects control corn oil containing low quantities of oxidized lipid, the levels of conjugated dienes in the chylomicron fraction were low (9.67 ±0.92 nmol//imol triglyceride), and no thiobarbituric acid-reactive substances (TBARS) could be detected. However, when subjects were fed a highly oxidized oil, the conjugated diene content in chylomicrons was increased 4.7-fold to 46±5.63 nmo\/fimo\ triglyceride, with 0.140±0.03 nmol TBARS//imol triglyceride. When subjects were fed mediumoxidized oil, the degree of oxidation of the chylomicron lipids was moderately increased (21.86 ±2.03 nmol conjugated Several observations suggest that oxidized lipoproteins are important in the development of atherosclerosis.' Incubation of oxidized lowdensity lipoprotein (LDL) with macrophages leads to formation of foam cells, whereas incubation with native LDL does not. Oxidized LDL is cytotoxic to endothelial cells and therefore could induce arterial wall injury. Finally, oxidized LDL stimulates the release of chemotactic proteins, cytokines, and growth factors from endothelial and other arterial wall cells, promoting the inflammatory milieu that characterizes atherosclerotic plaque. " Lipoprotein oxidation is postulated to occur within the microenvironment of the artery wall"; however, the source of oxidized lipoproteins in the serum of humans and animals has not been identified. Diet has been suggested as the source of oxidized lipoproteins in the intestinal lymph drainage of rodents.Studies in our laboratory have shown that the levels of oxidized lipids in the serum very-low-density lipoprotein (VLDL) plus LDL fraction of rats correlated with the quantity of oxidized lipids in the diet. Moreover, we observed a direct relation between the levels of oxidized lipid in the diet and the amounts of oxidized lipid in mesenteric lymph chylomicrons, suggesting that in rats oxidized lipids in the diet are absorbed by the small intestine, packaged in chylomicrons, and transported to the bloodstream. Furthermore, our studies have shown that these oxidized chylomicrons are Received April 5, 1994; revision accepted September 22, 1994. From the Department of Veterans Affairs Medical Center and the Departments of Surgery and Medicine, University of California, San Francisco. Correspondence to Ilona Staprans, PhD, VA Medical Center (151L), 4150 Clement St, San Francisco, CA 94121. © 1994 American Heart Association, Inc. dienes//xmol triglyceride). Additionally, we found that chylomicrons isolated after ingestion of oxidized oil were more susceptible to CuSO4 oxidation than chylomicrons isolated after ingestion of the control oil. The lag time for oxidation decreased from 4.30±0.40 to 3.24±0.51 hours (/<.O5). These data demonstrate that in humans dietary oxidized lipids are absorbed by the small intestine, incorporated into chylomicrons, and appear in the bloodstream, where they contribute to the total body pool of oxidized lipid. (Arterioscler Thromb. 1994;14:1900-1905.)