Abstract
Physical activity is an efficient strategy to delay development of obesity and insulin resistance, and thus the progression of obesity/diabetes-related cardiomyopathy. In support of this, experimental studies using animal models of obesity show that chronic exercise prevents the development of obesity-induced cardiac dysfunction (cardiomyopathy). Whether exercise also improves the tolerance to ischemia-reperfusion in these models is less clear, and may depend on the type of exercise procedure as well as time of initiation. We have previously shown a reduction in ischemic-injury in diet-induced obese mice, when the exercise was started prior to the development of cardiac dysfunction in this model. In the present study, we aimed to explore the effect of exercise on ischemic-tolerance when exercise was initiated after the development obesity-mediated. Male C57BL/6J mice were fed a high-fat diet (HFD) for 20–22 weeks, where they were subjected to high-intensity interval training (HIT) during the last 3 weeks of the feeding period. Sedentary HFD fed and chow fed mice served as controls. Left-ventricular (LV) post-ischemic functional recovery and infarct size were measured in isolated perfused hearts. We also assessed the effect of 3-week HIT on mitochondrial function and myocardial oxygen consumption (MVO2). Sedentary HFD fed mice developed marked obesity and insulin resistance, and demonstrated reduced post-ischemic cardiac functional recovery and increased infarct size. Three weeks of HIT did not induce cardiac hypertrophy and only had a mild effect on obesity and insulin resistance. Despite this, HIT improved post-ischemic LV functional recovery and reduced infarct size. This increase in ischemic-tolerance was accompanied by an improved mitochondrial function as well as reduced MVO2. The present study highlights the beneficial effects of exercise training with regard to improving the ischemic-tolerance in hearts with cardiomyopathy following obesity and insulin resistance. This study also emphasizes the exercise-induced improvement of cardiac energetics and mitochondrial function in obesity/diabetes.
Highlights
Cardiovascular disease is a major cause of morbidity and mortality in type 2 diabetic patients (Kannel and McGee, 1979)
We aimed to explore the cardiac effect of exercise training with regard to improving ischemic-tolerance in a model with obesitymediated cardiomyopathy
Sedentary mice fed an obesogenic diet for 20–22 weeks (HFDSED) developed obesity as indicated by elevated bodyweight and perirenal fat mass when compared to chow fed control (CON) mice (Table 1)
Summary
Cardiovascular disease is a major cause of morbidity and mortality in type 2 diabetic patients (Kannel and McGee, 1979). Obese and diabetic patients are at risk of developing a specific cardiomyopathy. The pathogenesis of this cardiomyopathy is multifactorial and complex, including fibrosis, inflammation, mitochondrial dysfunction, altered substrate utilization, oxidative stress and altered Ca2+ handling (Bugger and Abel, 2014; Jia et al, 2018). The pathophysiological mechanisms contributing to ischemic injury in normal hearts has been subject to a comprehensive investigation, the underlying mechanisms leading to the higher ischemic susceptibility in the diabetic heart are not well known. As increased oxygen consumption will be disadvantageous under conditions of limited oxygen availability, there is reason to suggest that the obesity/diabetes-induced increase in MVO2 contributes to a higher susceptibility to ischemic-reperfusion injury
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