Chylomicron remnant cholesteryl esters as the major constituent of very low density lipoproteins in plasma of cholesterol fed rabbits

Feeding rabbits 500 mg of cholesterol daily for 4 to 15 days greatly increased the concentrations of esterified cholesterol in lipoproteins of d<1.006 g/ml. The origin of hypercholesterolemic very low density lipoproteins was investigated by monitoring the degradation of labeled lymph chylomicrons administered to normal and cholesterol fed rabbits. Chylomicrons were labeled in vivo by feeding either 1) [³H]cholesterol and [¹⁴C]oleic acid or 2) [¹⁴C] cholesterol and [³H]retinyl acetate. After intravenous injection of labeled chylomicrons to recipient rabbits, [¹⁴C]triglyceride hydrolysis was equally rapid in normal and cholesterol fed animals. Normal rabbits rapidly removed from plasma both labeled cholesteryl and retinyl esters, whereas cholesterol fed rabbits retained nearly 50% of doubly labeled remnants in plasma 25 min after chylomicron injection. Ultracentrifugal separation of plasma into subfractions of very low density lipoproteins showed that chylomicron remnants in cholesterol fed animals are found among all subclasses of very low density lipoproteins. Analysis of cholesteryl ester specific activity time curves for the very low density lipoproteins subfraction from hypercholesterolemic plasma showed that nearly all esterified cholesterol in large very low density lipoproteins and approximately 30% of esterified cholesterol in small very low density lipoproteins was derived from chylomicron degradation. Apparently, nearly two thirds of the esterified cholesterol in total very low density lipoproteins from moderately hypercholesterolemic rabbits is of dietary origin.