Establishment of a mouse model of TMAO-induced cardiac injury and application of MICT intervention.

BACKGROUND

This study aims to explore the establishment of an animal model of cardiac injury induced by trimethylamine-N-oxide (TMAO), a metabolite secreted by gut microorganisms, and to investigate its application in moderate-intensity continuous training (MICT) intervention.

METHODS

C57BL6/J mice were randomly divided into four groups: normal mice (Nor, n = 15); mice administered TMAO (TMAO, n = 15); mice undergoing (Nor+MICT, n = 15); mice undergoing (MICT) and administered TMAO (TMAO+MICT, n = 15). Mice in the TMAO and TMAO+MICT groups received daily gavage of high-dose TMAO for 8 weeks, whereas those in the Nor+MICT and TMAO+MICT groups underwent MICT for 8 weeks (60 min per session, 5 days per week, at 50% maximal running capacity). Cardiac function was evaluated using ultrasound, myocardial histology was examined using hematoxylin and eosin (HE) staining, and nuclear magnetic resonance (NMR)-based metabolomics was employed for multivariate statistical and metabolic pathway analyses.

RESULTS

Relative to the Nor group, TMAO-treated mice exhibited significant weight loss, elevated heart rate, and reduced ejection fraction and left ventricular fractional shortening, indicating cardiac impairment. Importantly, the TMAO+MICT group demonstrated significant improvements in these parameters compared to the TMAO group, alongside distinct alterations in myocardial metabolic profiles. TMAO altered five metabolic pathways relative to controls, whereas MICT induced significant changes in three pathways in TMAO-treated mice.

CONCLUSION

Eight weeks of high-dose TMAO administration induced significant cardiac dysfunction in mice, which was effectively mitigated by MICT intervention. Consequently, this animal model serves as a valuable tool for investigating the mechanisms underlying the impact of MICT on cardiovascular diseases.