Absorption of dietary cholesterol oxidation products and incorporation into rat lymph chylomicrons

Abstract

Cholesterol oxidation products (oxysterols) induce macrophage lipid loading and accumulate in early arterial fatty streaks. The origin of lesion oxysterols has not been elucidated. The absorption of oxysterols from the diet and transport to the arterial wall by postprandial lipoprotein remnants may be a significant source. This study aimed to investigate the extent of oxysterol absorption and the effect on chylomicron composition. Cholesterol was heat-treated, causing 30% oxidation; the major oxidation products were 7 beta-hydroxycholesterol, 7-keto-cholesterol, 5 alpha,6 alpha-epoxycholesterol, and 5 beta,6 beta-epoxycholesterol. Conscious lymph-cannulated rats were given a bolus gastric infusion 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 chylomicrons. Rats given pure cholesterol had no increase in oxysterols above baseline levels. The incorporation of oxysterols into lymph chylomicrons 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-epoxy-cholesterol at 5 h. The absorption of oxysterols in animals given the oxidized cholesterol gastric infusate was associated with lymph chylomicron compositional changes at 2-4 h. The oxidized cholesterol-treated group had a twofold increase in the cholesterol (890 +/- 84 micrograms vs. 440 +/- 83 microgram at 3 h) and triglyceride content (19.76 +/- 3.4 micrograms vs. 8.49 +/- 3.8 micrograms at 3 h). This led to a doubling of chylomicron size over this postprandial period, with particles having a mean diameter of 294 nm in the oxidized cholesterol-treated animals, compared to 179 nm in the purified cholesterol group. In conclusion, dietary 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 possible deposition in arterial lesions.