Regulation of serum apolipoprotein E metabolism: role of chylomicron metabolism.

The mechanism by which high-fat, high-cholesterol diets lower serum apolipoprotein E (apoE) concentration was studied in rats by feeding a single high-fat, high-cholesterol meal and by intravenously infusing chylomicrons containing low and high amounts of cholesterol. Serum apoE concentrations were unchanged 9 hours after an olive oil meal but were decreased by 35% after an olive oil/cholesterol-enriched meal. The decrease in serum apoE concentrations with the olive oil/cholesterol meal was accompanied by a decrease in apoE concentration in the high density lipoprotein fraction. Three hours after the intravenous infusion of cholesterol-enriched chylomicrons, serum apoE concentrations decreased 40%, whereas serum apoE concentrations decreased by only 10% when chylomicrons with low cholesterol concentrations or saline were infused. It is concluded that the metabolism of cholesterol-enriched chylomicrons results in an increased removal of serum apoE and that the cholesterol content of chylomicrons is a determinant of serum apoE removal.