Fat feeding in humans induces lipoproteins of density less than 1.006 that are enriched in apolipoprotein [a] and that cause lipid accumulation in macrophages.

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Abstract

Formula diets containing lard or lard and egg yolks were fed to six normolipidemic volunteers to investigate subsequent changes in the composition of lipoproteins of d less than 1.006 g/ml and in their ability to bind and be taken up by receptors on mouse macrophages. Both formulas induced the formation of d less than 1.006 lipoproteins that were approximately 3.5-fold more active than fasting very low density lipoproteins (VLDL) in binding to the receptor for beta-VLDL on macrophages. Subfractionation of postprandial d less than 1.006 lipoproteins by agarose chromatography yielded two subfractions, fraction I (chylomicron remnants) and fraction II (hepatic VLDL remnants), which bound to receptors on macrophages. However, fraction I lipoproteins induced a 4.6-fold greater increase in macrophage triglyceride content than fraction II lipoproteins or fasting VLDL. Fraction I lipoproteins were enriched in apolipoproteins (apo) B48, E, and [a]. Fraction II lipoproteins lacked apo[a] but possessed apo B100 and apo E. The apo[a] was absent in normal fasting VLDL, but was present in the d less than 1.006 lipoproteins (beta-VLDL) of fasting individuals with type III hyperlipoproteinemia. The apo[a] from postprandial d less than 1.006 lipoproteins was larger than either of two apo[a] subspecies obtained from lipoprotein (a) [Lp(a)] isolated at d = 1.05-1.09. However, all three apo[a] subspecies were immunochemically identical and had similar amino acid compositions: all were enriched in proline and contained relatively little lysine, phenylalanine, isoleucine, or leucine. The association of apo[a] with dietary fat-induced fraction I lipoproteins suggests that the previously observed correlation between plasma Lp(a) concentrations and premature atherosclerosis may be mediated, in part, by the effect of apo[a] on chylomicron remnant metabolism.

Authors

T P Bersot, T L Innerarity, R E Pitas, S C Rall Jr, K H Weisgraber, R W Mahley