Effect of a Dual Intervention with Vitamin D Supplementation and Voluntary Physical Exercise on Cardiac Remodeling and Function in a Mouse Model of Diet-Induced Type 2 Diabetes

Effect of a Dual Intervention with Vitamin D Supplementation and Voluntary Physical Exercise on Cardiac Remodeling and Function in a Mouse Model of Diet-Induced Type 2 Diabetes. Cardiology and Cardiovascular Medicine 6 229-236. Abstract Background and Aims: We have previously demonstrated the cardiac beneficial effects of vitamin D (VD) supplementation. The aim of this study was to evaluate the combined effects of voluntary Physical Exercise (PE) and VD on cardiac remodeling and function in tertiary prevention in a mice model of diet-induced diabetes. Methods and Results: Mice were fed with a high fat and sucrose diet for 10 weeks. Then, they were divided into 4 subgroups for the 15 following weeks: diet, diet/vitamin D, diet/PE and diet/VD/PE. Glucose homeostasis assessment and echocardiography were performed one week before the end of the protocol. Blood samples and hearts were collected at sacrifice. After 25 weeks of diet alone, obese mice displayed diabetes, cardiac concentric hypertrophy combination improved glucose homeostasis and was associated with physiological cardiac remodeling, with however no additional beneficial effect over PE or VD alone on cardiac function. Conclusion: The major finding of the present study is that VD supplementation and PE exert similar cardioprotective effects in diabetic mice, with no major synergistic effect from their combination. Abstract The present study is the first to investigate the combined effects of voluntary PE and VD supplementation on cardiac remodeling and function in tertiary prevention in a rodent model of diet-induced T2D. Numerous studies demonstrated beneficial effects of voluntary PE or exercise training on cardiac function in pharmacological [17] or diet-induced [14] rodent models of diabetes, agreeing with our results. Data regarding the effects of VD are scarce [11]. The salient finding from our study is that VD supplementation exerts similar favorable effects to PE on both regional and global cardiac function while their combination did not yield to additional benefits. Since VD and PE were each other already able to normalize cardiac function, synergic effects were unlikely to be expected. Of note, PE or VD individually prevented the development of HFS-induced pathological cardiac remodeling, in accordance with previous studies [9, 17]. Interestingly, their combination yielded to cardiac hypertrophy, similar in magnitude to that one seen in HFS mice, although physiological. The underlying mechanisms associated with improvements in cardiac remodeling and function consecutive to PE or VD imply very likely favorable changes at both systemic and cardiac levels in signaling pathways related to inflammation and oxidative stress [18] leading to enhancement in cardiac metabolism, calcium handling, apoptosis and fibrosis [19, 20]. Aside, we also demonstrated cardioprotective effects of VD through modulation of cardiac lipotoxicity [11]. Further investigations will be needed to properly characterize the remodeling related to PE combined to VD and to define the underlying mechanisms responsible for enhancement in regional function. Altogether, our results further emphasize the cardioprotective value of interventions with VD and PE in cardiometabolic diseases.