Organization of the core lipids of lipoproteins from normal and cholesterol-fed rabbits. A proton nuclear magnetic resonance study.

Abstract

When rabbits are fed a diet supplemented with cholesterol, their plasma cholesterol levels increase markedly, and they develop atherosclerosis. Most of the plasma cholesterol exists as cholesteryl esters in very low density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL). The triglyceride content of the lipoprotein cores decreases sharply during cholesterol feeding. This change is most marked for VLDL in which it decreases from 74% to 5%, while the cholesteryl ester content increases from 26% to 95%. The IDL and low-density lipoprotein (LDL) fractions from cholesterol-fed rabbits have a triglyceride content of 2% or less in their cores. The mobility of the core cholesteryl esters has been studied by proton nuclear magnetic resonance spectroscopy. Changes in the mobility were assessed by measuring the temperature dependence of the amplitude of the methylene resonances. The decrease in spectral amplitude for VLDL, IDL, and LDL from cholesterol-fed rabbits between 55 and 15 degrees C shows that the mobility of the core cholesteryl esters is temperature dependent and that the cholesteryl esters display thermal order--disorder transitions with midpoints of 42, 40, and 38 degrees C, respectively. At physiological temperatures, the core cholesteryl esters of lipoproteins from cholesterol-fed rabbits therefore exist in a partially ordered state. In contrast, the core cholesteryl esters of VLDL, IDL, and LDL from normal rabbits show no evidence for an order--disorder transition. This is consistent with their high core triglyceride content which precludes the existence of an ordered cholesteryl ester phase within the core. The core cholesteryl esters of normal rabbit lipoproteins therefore exist in a liquid state at physiological temperatures. High-density lipoproteins (HDL) from normal and cholesterol-fed rabbits fail to display an order--disorder transition. This is attributed to the constraints imposed by the small HDL core diameter, which prevents the existence of an ordered arrangement of cholesteryl esters, irrespective of the core triglyceride content.