Addition of arginine but not glycine to lysine plus methionine-enriched diets modulates serum cholesterol and liver phospholipids in rabbits

Previous experiments from our laboratory showed that in rabbits fed an amin o acid diet corresponding to 30% casein, enrichment of the diet with L-lysi ne and L-methionine caused a marked increase in serum total and LDL cholest erol levels as well as a substantial body weight loss, Both effects were pa rtially prevented by supplementation with L-arginine. The present studies w ere designed to extend this earlier observation by assessing the role of di fferent dietary amino acids in modulation of cholesterolemic responses and body weights. In the first experiment, the original lysine and methionine-e nriched diet was supplemented with glycine in an attempt to modify methioni ne metabolism, and thus to reduce body weight loss. In addition, the mechan ism of action of lysine and methionine was investigated by quantitation of major liver phospholipids. The results showed that glycine addition had no effect on weight loss or hypercholesterolemia, nor did it alter plasma leve ls of homocyst(e)ine, an intermediate in methionine metabolism. However, en richment of the diet with lysine and methionine (with or without glycine) s ignificantly increased liver levels of phosphatidylcholine and the ratio of phosphatidylcholine to phosphatidylethanolamine, apparently through increa sed enzymatic conversion. These changes were consistent with higher lipopro tein levels and thus may explain the hypercholesterolemia. A second experim ent showed that similar effects on body weights and serum cholesterol could be obtained by adding lysine and methionine to a diet containing amino aci ds equivalent to only 15% casein, or 15% intact casein. This approach is mo re physiologic and also reduces the expense of experiments designed to stud y the effects of lysine and methionine in more detail.