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.
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.
D000328:Adult; D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D004530:Egg Yolk; D005260:Female; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000097:blood* / Q000302:isolation & purification; D008079:Lipoproteins, VLDL / Q000097:blood*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D014280:Triglycerides / Q000378:metabolism
D001053:Apolipoproteins; D004041:Dietary Fats; D017270:Lipoprotein(a); D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol; C029310:lard