LDL versus apolipoprotein B responses to variable proportions of selected amino acids in semipurified diets fed to rabbits and in the media of HepG2 cells

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Rabbits fed amino acid diets containing high proportions of several essential amino acids (EAA), mainly Lys and Met, develop hypercholesterolemia associated with elevated low density lipoprotein (LDL) cholesterol and apoprotein B (apo B) levels. This effect is partially prevented by feeding a high proportion of Arg. We previously demonstrated that down-regulation of hepatic LDL receptors contributes to elevation of LDL produced by selected EAA. Additionally, our earlier studies and recent observation in transformed liver cells HepG2 suggested that amino acids can alter apo B production, and that direct interaction between amino acids and hepatic cells is likely to be involved in the mechanism. Presently, these hypotheses were further examined. Our experiment in vivo demonstrated that rates of incorporation of 14C-Lys into LDL apoprotein were elevated in rabbits fed hypercholesterolemic Lys- and Met-enriched diet compared with normocholesterolemic animals fed diets enriched with Lys and Leu. This suggested that increase in hepatic apo B production contributed to hypercholesterolemic response induced by the experimental diet. In vitro, we used HepG2 cells to investigate whether exposure of these cells to amino acid mixtures similar to those tested in rabbits can induce changes in apo B consistent with LDL responses found in vivo. These results showed that apo B responses in cell culture corresponded with LDL changes observed in rabbits in relation to effects of Arg, but not to those of hypercholesterolemic EAA. This suggests that HepG2 cells provide a useful model for studying the mechanism of regulation of apo B metabolism by dietary Arg but not of the regulation by other dietary amino acids.