Impact of dietary choline on homocysteine metabolism in atherosclerosis prone mice

Aim. Scientific evidence revealed that a positive correlation existsbetween cardiovascular risk and plasma levels of TMAO, a productof dietary choline metabolism. This study was aimed at investigat-ing whether dietary choline affects additional metabolic pathwaysbesides that leading to TMAO production.Methods. Ten-week-old EKO female mice were fed for 16 weekstwo standard rodent diets differing for a low (0.09%) or high (1.2%)choline content. Atherosclerosis development was quantified at theaortic sinus, targeted plasma metabolomic and hepatic gene ex-pression were performed. Additionally, in vitro experiments onHepG2 cells were set up to elucidate the mechanism by which cho-line alters plasma metabolome.Results. High choline intake was associated with greater athero-sclerosis development and increased plasma levels of TMAO. Inter-estingly, high choline feeding was associated with lower plasmalevels of homocysteine and a concomitant increase of its relatedmetabolites, methionine, sarcosine and glycine. Hepatic gene ex-pression of Aldh7a1, Slc44a1, Sardh and Gnmt was increased inEKO mice fed high-choline diet, supporting the metabolic findings.In vitro experiments showed that several pathways are devoted tohomocysteine metabolism and can be mutually regulated by actingon enzymes belonging to different synthetic routes.Conclusions. Our data confirm that an increased dietary intake ofcholine worsens atherosclerosis burden and leads to increasedplasma TMAO levels. Interestingly, choline intake also modulatesmetabolic processes affecting plasma concentrations of homocyste-ine as well as methionine, sarcosine, and glycine. These observa-tions offer new insights into the understanding of how cholinemight influence atherosclerosis development and modify cardio-vascular risk.