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

Abstract

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.

Keywords:

• TMAO
• choline
• gut microbiota
• bile acid
• atherosclerosis

Acknowledgements

The authors thank Wei-Qing Tang for excellent technical assistance.

Geolocation information

This work was conducted in NO. 1 DaHua Road, Dong Dan, Beijing 100730, P.R. China.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability Statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by Beijing Natural Science Foundation (grant number 7214250 and 7222156), and the CAMS Innovation Fund for Medical Sciences 2021-I2M-1-050).