EFFECT OF HIGH-LEVELS OF SELECTED DIETARY ESSENTIAL AMINO-ACIDS ON HYPERCHOLESTEROLEMIA AND DOWN-REGULATION OF HEPATIC LDL RECEPTORS IN RABBITS

Earlier studies showed that the elevation of serum total and low density lipoprotein (LDL) cholesterol levels produced in rabbits by feeding high levels of a casein amino acid mixture in a cholesterol-free, semipurified diet was due primarily to the essential amino acids (EAA) in the mixture. Replacing all of the non-essential amino acids in the mixture by glutamic acid (45% EAA + Glu) had little effect on the hypercholesterolemia produced by the EAA. Experiments designed to identify the hypercholesterolemic EAA showed that (i) feeding high levels of ketogenic EAA only (45% EketoAA) gave a substantial but variable elevation of serum total and LDL cholesterol and (ii) feeding high levels of all EAA except arginine (45% EAA-Arg) gave a particularly strong hypercholesterolemic response. In rabbits fed the 45% EAA-Arg diet and to a lesser extent, in those fed the 45% EAA + Glu diet, EDTA-sensitive binding of I-125-LDL to hepatic membranes in vitro was reduced compared to a control, low-cholesterolemic group fed all essential and non-essential amino acids at a level corresponding to 14.7% casein, indicating that the hypercholesterolemia was associated with down-regulation of hepatic LDL receptors.