High- and Moderate-Intensity Training Normalizes Ventricular Function and Mechanoenergetics in Mice With Diet-Induced Obesity

Abstract

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.

Exercise training promotes cardioprotection through oxygen-sparing action in high fat-fed mice

“…At the end of perfusion, myocardial reactive oxygen species (ROS) content was measured in LV tissue stained with dehydroethidium (15-m cryosections) as previously described (20). Quantitative analysis of myocardial collagen content was performed by HPLC analysis of myocardial hydroxyproline using the AccQ-Fluor reagent kit (Waters, Milford, MA) as previously described (30) with some modifications (1).…”

“…Following 8 wk of high-fat feeding, HFD mice were assigned to sedentary lifestyle (HFD SED, n ϭ 18) or high-intensity treadmill running 5 days/wk for 10 wk (HFD HIT, n ϭ 20) as previously described by Hafstad et al (20). The exercise protocol was 10 bouts of 4-min, high-intensity, treadmill running at 25°inclination, corresponding to 85-90% of V O2max, interspersed by 2 min active rest.…”

“…Real-time quantitative PCR analysis was performed on LV tissue samples using an ABI PRISM 7900 HT Fast real-time thermal cycler as previously described (20).…”

“…Exercise training also improved mechanical efficiency and counteracted the development of ventricular dysfunction and remodeling (20). The aim of the present study was to examine whether exercise has an oxygen-sparing effect in an obese model with less severe ventricular dysfunction and to examine whether this will increase the tolerance to ischemiareperfusion injury.…”

“…We have previously demonstrated that exercise training reverses oxygen wasting in hearts from diet-induced obese mice subjected to a dietary regime that led to diastolic and systolic ventricular dysfunction, as well as concentric remodeling (20). Exercise training also improved mechanical efficiency and counteracted the development of ventricular dysfunction and remodeling (20).…”