High-choline diet exacerbates cardiac dysfunction, fibrosis, and inflammation in a mouse model of heart failure with preserved ejection fraction.

Abstract Background Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite of dietary choline and other trimethylamine-containing nutrients, has been associated with a poor prognosis for patients with cardiovascular disease (CVD). However, the role and underlying mechanisms of TMAO in the cardiac function of patients with heart failure with preserved ejection fraction (HFpEF) have not been elucidated. Methods and Results C57BL/6 mice were fed a normal diet, high-choline (1.2%) diet and/or 3-dimethyl-1-butanol (DMB) diet three weeks prior to the operation (uninephrectomy followed by a continuous saline or aldosterone infusion). Mice were assessed for four weeks after the operation. Echocardiographic and hemodynamic measurements were performed. Blood samples were evaluated for choline, TMAO, and inflammatory factor levels. Left ventricular (LV) tissues were collected to assess myocardial fibrosis and inflammation. LV hypertrophy, pulmonary congestion, and diastolic dysfunction were markedly exacerbated in HFpEF mice fed high-choline diets compared with mice fed the control diet. Myocardial fibrosis and inflammation were markedly increased in HFpEF mice fed high-choline diets compared with animals fed the control diet. Additionally, DMB markedly ameliorated cardiac diastolic dysfunction, myocardial fibrosis and inflammation in the choline-fed HFpEF mice. Conclusions A high-choline diet exacerbates cardiac dysfunction, myocardial fibrosis, and inflammation in HFpEF mice, and DMB ameliorates the high-choline diet-induced cardiac remodeling.