DIETARY CHOLINE SUPPLEMENTATION INCREASES THE PLASMA CONCENTRATION OF SEVERAL AMINO ACIDS DURING ATHEROSCLEROSIS DEVELOPMENT

Background and Aims: Increased dietary intake of choline worsens the development of atherosclerosis in ApoE-KO mice. Gut microbial metabolism of choline results in the production of trimethylamine, which, upon intestinal absorption is converted into the pro-atherogenic molecule trimethylamine-N-oxide (TMAO) in the liver. In this study we investigated if additional endogenous plasma metabolites were modulated by increased choline intake. Methods: Eight weeks old ApoE-KO female mice (n=20/group) were fed for 16 weeks on standard rodent diets containing low (0.09%) or high concentration (1.2%) choline. At sacrifice, atherosclerosis was evaluated, and a targeted metabolomics of plasma was performed. Results: The boost of dietary choline caused a worsening of atherosclerosis development at the aortic sinus. As expected, the increased choline intake was accompanied by a significantly increased plasma concentration of TMAO. Less obviously, in the group of mice that received high-dose choline, an increased plasma concentration of carnitine, a branched nonessential amino acid endogenously synthesized in kidney and liver that plays a role in energy metabolism, was detected. Similarly, in the same mice, an increased plasma concentration of the amino acids serine, glycine, methionine and sarcosine with a concomitantly reduced concentration of homocysteine was observed, suggesting an impairment in several interrelated metabolic pathways such as the methionine cycle, folate cycle, sarcosine pathway and transsulfuration pathway. Conclusions: Our results indicate that, in addition to increasing TMAO, dietary choline supplementation leads to increased plasma concentration of several amino acids with key roles in different metabolic pathways. Such alterations may reveal further choline-mediated deleterious effects predisposing to atherosclerosis.