ABSORPTION OF DIETARY-CHOLESTEROL OXIDATION-PRODUCTS AND INCORPORATION INTO RAT LYMPH CHYLOMICRONS

Cholesterol oxidation products (oxysterols) in duce macrophage lipid l oading and accumulate in early arterial fatty streaks. The origin of l esion oxysterols has not been elucidated. The absorption of oxysterols from the diet and transport to the arterial wall by postprandial lipo protein remnants may be a significant source. This study aimed to inve stigate the extent of oxysterol absorption and the effect on chylomicr on composition. Cholesterol was heat-treated, causing 30% oxidation; t he major oxidation products were 7 beta-hydroxycholesterol, 7-ketochol esterol, 5 alpha,6 alpha-epoxycholesterol, and 5 beta,6 beta-epoxychol esterol. Conscious lymph-cannulated rats were given a bolus gastric in fusion of 50 mg oxidized cholesterol or 50 mg purified cholesterol in a vehicle of triglyceride. In the rats given the oxidized cholesterol, 6% of the oxysterol load was absorbed and incorporated into lymph chy lomicrons. Rats given pure cholesterol had no increase in oxysterols a bove baseline levels. The incorporation of oxysterols into lymph chylo microns differed over time with 7 beta-hydroxycholesterol, having peak absorption at 3 h, followed by 7-ketocholesterol at 4 h and 5 alpha,6 alpha-epoxycholesterol at 5 h. The absorption of oxysterols in animal s given the oxidized cholesterol gastric infusate was associated with lymph chylomicron compositional changes at 2-4 h. The oxidized cholest erol-treated group had a twofold increase in the cholesterol (890 +/- 84 mu g vs. 440 +/- 83 mu g at 3 h) and triglyceride content (19.76 +/ - 3.4 mu g vs. 8.49 +/- 3.8 mu g at 3 h). This led to a doubling of ch ylomicron size over this postprandial period, with particles having a mean diameter of 294 nm in the oxidized cholesterol treated animals, c ompared to 179 nm in the purified cholesterol group. In conclusion, di etary oxysterols appear to influence postprandial lipoprotein particle size and composition. These changes may have effects on the clearance of chylomicrons from plasma, arterial delivery of oxysterols, and pos sible deposition in arterial lesions.