Moderate- and High-Intensity Endurance Training Alleviate Diabetes-Induced Cardiac Dysfunction in Rats

Abstract

Exercise training is an encouraging approach to treat cardiac dysfunction in type 2 diabetes (T2DM), but the impact of its intensity is not understood. We aim to investigate whether and, if so, how moderate-intensity training (MIT) and high-intensity interval training (HIIT) alleviate adverse cardiac remodeling and dysfunction in rats with T2DM. Male rats received standard chow (n = 10) or Western diet (WD) to induce T2DM. Hereafter, WD rats were subjected to a 12-week sedentary lifestyle (n = 8), running MIT (n = 7) or HIIT (n = 7). Insulin resistance and glucose tolerance were assessed during the oral glucose tolerance test. Plasma advanced glycation end-products (AGEs) were evaluated. Echocardiography and hemodynamic measurements evaluated cardiac function. Underlying cardiac mechanisms were investigated by histology, western blot and colorimetry. We found that MIT and HIIT lowered insulin resistance and blood glucose levels compared to sedentary WD rats. MIT decreased harmful plasma AGE levels. In the heart, MIT and HIIT lowered end-diastolic pressure, left ventricular wall thickness and interstitial collagen deposition. Cardiac citrate synthase activity, mitochondrial oxidative capacity marker, raised after both exercise training modalities. We conclude that MIT and HIIT are effective in alleviating diastolic dysfunction and pathological cardiac remodeling in T2DM, by lowering fibrosis and optimizing mitochondrial capacity.

Moderate-Intensity and High-Intensity Interval Exercise Training Offer Equal Cardioprotection, with Different Mechanisms, during the Development of Type 2 Diabetes in Rats

“…In this model, the WD for 18 weeks led to weight gain, insulin resistance and disturbed glucose tolerance, as well as cardiac complications, including LV hypertrophy and increased EDP, while the EF remained preserved. When the WD regime was continued, the rats displayed hypertension, increased ESV and pronounced reduction in EF by 30 weeks [17]. Metabolically, we have now shown that both MIT and HIIT are able to prevent the development of insulin resistance and improved glucose tolerance in WD-fed rats, confirming results in clinical trials on patients at risk for T2DM, as has been reviewed elsewhere [29].…”

“…In diabetic cardiomyopathy, excessive formation of LV interstitial fibrosis is one of the main disease hallmarks and underlies pathological concentric remodeling [3]. We and others have previously shown that MIT and HIIT have therapeutically decreased interstitial fibrosis content in the LV areas of diet-induced T2DM rats with cardiac dysfunction [17,38,42]. Here, we have validated these findings in preventive settings, as both exercise training modalities reduced LV interstitial fibrosis.…”

“…A cross-sectional study by Maessen et al has described how lifelong endurance athletes have lower circulating MGO compared with sedentary controls [49]. Preclinically, we have shown that HIIT has decreased plasma AGEs in WD-induced T2DM rats [17]. MIT has also attenuated the accumulation of total AGE content in the myocardia of aging rats [50].…”

“…In the heart, physiological eccentric hypertrophy, characterized by a mild increase in LV size and preserved cardiac morphology and function, can develop in response to endurance training [30]. However, we have previously demonstrated that 12-week MIT and HIIT have reversed pathological concentric hypertrophy, characterized by increased PWT, heart weight and cardiac fibrosis, in WD-fed rats [17]. The potential of endurance exercise training to treat pathological concentric hypertrophy has also been confirmed in a randomized controlled trial that showed that high-intensity exercise training reduced LV myocardial stiffening in HFpEF patients with LV septal hypertrophy [31].…”

“…The underlying mechanisms responsible for cardiac improvements after endurance exercise training, predominantly MIT, have been investigated in genetically, chemically and high-fat diet (HFD)-induced T2DM animal models and reviewed elsewhere [15,16]. We recently demonstrated that both MIT and HIIT reverse adverse cardiac remodeling and cardiac dysfunction by lowering myocardial fibrosis and improving mitochondrial oxidative capacity in rats with high-sugar-or so-called Western-diet (WD)-induced T2DM [17]. Up to now, experimental studies have mainly explored the therapeutic effect of endurance exercise training, describing its impact after T2DM diagnosis, on the cardiac phenotype.…”