Abstract
Excessive consumption of western diet (WD) induces obesity, resulting in cardiac dysfunction. Voluntary exercise ameliorates WD-induced obesity, but its effect on cardiac dysfunction remains unclear. Recent evidence suggests that elevated trimethylamine N-oxide (TMAO), a gut microbe-derived metabolite, can impair cardiac function in WD-induced obesity. We hypothesized that cardiac dysfunction in WD-induced obesity would be prevented by voluntary exercise but abolished by TMAO supplementation. Male CD1 mice fed a WD were assigned to sedentary, exercise or exercise with TMAO treatment for 8 weeks. Male CD1 mice fed a normal diet (ND) for 8 weeks were assigned to sedentary (control). Compared with ND-sedentary mice, WD-sedentary mice gained significantly more body weight and displayed metabolic abnormalities at the end of the experiment. Echocardiography showed significantly impaired cardiac systolic and diastolic function in WD-induced obese mice. Voluntary exercise partially attenuated weight gain and metabolic disorders, but completely prevented cardiac dysfunction in WD-induced obese mice. Molecular studies revealed that WD-sedentary mice had elevated plasma TMAO levels, along with increased myocardial inflammation and fibrosis, all of which were inhibited by voluntary exercise. Of note, concomitant administration of TMAO had no effects on body weight and metabolic disorders, but it abolished the beneficial effects of voluntary exercise on cardiac dysfunction, myocardial inflammation, and fibrosis in WD-induced obese mice. The results suggest that voluntary exercise prevents cardiac dysfunction in WD-induced obesity by inhibiting myocardial inflammation and fibrosis. Moreover, the cardioprotective effects of voluntary exercise in WD-induced obesity can be abolished by TMAO supplementation, which abrogates voluntary exercise-induced changes in myocardial inflammation and fibrosis.
Highlights
Obesity has become a global health problem that is reaching epidemic proportions, regardless of gender and age (Flegal et al, 2012; Head, 2015)
After 6 weeks of Western diet (WD) feeding, WD-sedentary mice showed a significant increase in body weight compared with normal diet (ND)-sedentary mice and this trend continued throughout the dietary protocol
The major findings of the present study are as follows: (1) voluntary exercise attenuates but does not normalize WD-induced obesity and metabolic disorders in mice; (2) voluntary exercise in WD-induced obese mice prevents cardiac dysfunction, along with normalization of plasma trimethylamine N-oxide (TMAO) levels; (3) voluntary exercise in WD-induced obese mice inhibits myocardial fibrosis and inflammation; (4) administration of TMAO in WD-induced obese mice has no effects on metabolic parameters, but reverses voluntary exercise-induced changes in plasma TMAO levels and abrogates the beneficial effects of voluntary exercise on cardiac function, myocardial fibrosis and inflammation
Summary
Obesity has become a global health problem that is reaching epidemic proportions, regardless of gender and age (Flegal et al, 2012; Head, 2015). Obesity is a major risk factor for the development of many cardiovascular diseases, such as coronary heart disease, heart failure (HF), and stroke (Poirier et al, 2006; Zalesin et al, 2011; Pandey et al, 2015; Aune et al, 2016; Obokata et al, 2017). Voluntary Exercise and Cardiac Dysfunction study recently revealed that the associations of incident HF with overweight status and obesity are stronger than those for other cardiovascular disease subtypes and is unexplained by traditional risk factors (Ndumele et al, 2016). Several cohort studies showed that almost 60% of heart failure patients are overweight and that 35% are obese (Gustafsson et al, 2005). Experimental studies have demonstrated that WD-induced obese animals exhibit cardiac dysfunction (Carbone et al, 2015; Kesherwani et al, 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
