High- and moderate-intensity training normalizes ventricular function and mechanoenergetics in mice with diet-induced obesity.

Although exercise reduces several cardiovascular risk factors associated with obesity/diabetes, the metabolic effects of exercise on the heart are not well-known. This study was designed to investigate whether high-intensity interval training (HIT) is superior to moderate-intensity training (MIT) in counteracting obesity-induced impairment of left ventricular (LV) mechanoenergetics and function. C57BL/6J mice with diet-induced obesity (DIO mice) displaying a cardiac phenotype with altered substrate utilization and impaired mechanoenergetics were subjected to a sedentary lifestyle or 8-10 weeks of isocaloric HIT or MIT. Although both modes of exercise equally improved aerobic capacity and reduced obesity, only HIT improved glucose tolerance. Hearts from sedentary DIO mice developed concentric LV remodeling with diastolic and systolic dysfunction, which was prevented by both HIT and MIT. Both modes of exercise also normalized LV mechanical efficiency and mechanoenergetics. These changes were associated with altered myocardial substrate utilization and improved mitochondrial capacity and efficiency, as well as reduced oxidative stress, fibrosis, and intracellular matrix metalloproteinase 2 content. As both modes of exercise equally ameliorated the development of diabetic cardiomyopathy by preventing LV remodeling and mechanoenergetic impairment, this study advocates the therapeutic potential of physical activity in obesity-related cardiac disorders.