Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe –/– mice through different mechanisms

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe –/– mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe–/– mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

氧化三甲胺（Trimethylamine N-oxide, TMAO）是一种依赖肠道菌群的代谢产物，现已被证实可加重心血管疾病。然而，TMAO在心血管疾病进展中的作用机制仍不明确。本研究旨在探讨TMAO对动脉粥样硬化（atherosclerosis, AS）发生发展的影响及其潜在机制。载脂蛋白E敲除（Apoe–/–）小鼠在正常饮食与西式饮食模式下分别补充胆碱或TMAO，干预时长为12周。无论是正常饮食还是西式饮食组，补充胆碱或TMAO均显著促进了Apoe–/–小鼠的动脉粥样硬化斑块进展。此外，补充胆碱或TMAO可升高小鼠血清血脂水平，并增强主动脉根部的炎症反应。尤为关键的是，在西式饮食模式下补充胆碱或TMAO会改变小鼠肠道菌群组成与胆汁酸代谢。因此，在西式饮食喂养的小鼠中，补充胆碱或TMAO可能通过调控肠道菌群促进动脉粥样硬化；而在正常饮食喂养的小鼠中，则通过其他机制发挥作用，即便是正常饮食下补充胆碱或TMAO，同样可促进动脉粥样硬化进展。