Differences in apolipoprotein and lipid composition between human chylomicron remnants and very low density lipoproteins isolated from fasting and postprandial plasma.
Björkegren J., Karpe F., Milne RW., Hamsten A.
Triglyceride-rich lipoproteins (TRLs) that are modified during alimentary lipemia and their remnants are indicated to play an important role in the development of atherosclerosis. Although recent studies in transgenic and gene knock-out animal models have shed new light on the function of different apolipoproteins (apos) in the metabolism of TRLs and on their respective role in atherogenesis in these models, little is known about the compositional properties of human chylomicron remnants and very low density lipoprotein (VLDL). To address this issue, apos E, C-I, C-II, and C-III and lipids (triglycerides, phospholipids and cholesterol) were measured in Svedberg flotation rate (Sf) 60-400 and Sf 20-60 subfractions of VLDL and chylomicron remnants isolated from fasting and postprandial plasma samples in ten normotriglyceridemic men. VLDL was separated from chylomicron remnants by immunoaffinity chromatography using monoclonal antibodies (4G3 and 5E11) recognizing apoB-100 but not apoB-48 epitopes. The triglyceride, cholesterol and apoC-II contents of large (Sf 60-400) chylomicron remnants were significantly higher compared with large VLDL particles, while the small (Sf 20-60) chylomicron remnants contained significantly more apoC-II molecules but fewer apoC-I molecules than small VLDL. Whereas the apoC-III contents of large chylomicrons decreased, the apoC-III contents of large VLDL increased postprandially. The cholesterol to triglyceride ratio of large VLDL particles increased transiently by 50% in response to the oral fat load, whereas the cholesterol to triglyceride ratio of large chylomicron remnant particles and small TRL remnants increased 50-100% throughout the entire postprandial period. The specific alterations of the apolipoprotein and lipid composition of chylomicron remnants and VLDL particles observed during alimentary lipemia are likely to target these lipoprotein species differently to metabolic routes and to confer both endogenous and exogenous remnant lipoprotein roles in atherogenesis.