Molecular mechanisms underlying fructose-induced cardiovascular disease: exercise, metabolic pathways, and microRNAs.

NEW FINDINGS What is the central question of this study? What are the mechanisms underlying the cardiac protective effect of aerobic training in the progression of a high fructose-induced cardiometabolic disease in Wistar rats? What are the main findings and their importance? At the onset of cardiovascular disease, aerobic training activates the p-p70s6k, ERK, and the IRs-PI3K-AKT pathways, without changing the miR-126 and miR-195 levels, therefore, providing evidence that aerobic training modulates the insulin signalling pathway. This data contributes to the understanding of the molecular cardiac changes that are associated with physiological left ventricular hypertrophy during the development of a cardiovascular disease. ABSTRACT Introduction: During the onset of cardiovascular disease (CVD), disturbances in myocardial vascularisation, cell proliferation, and protein expression are observed. Aerobic training prevents CVD but the underlying mechanisms behind left ventricle hypertrophy are not fully elucidated. AIM To investigate the mechanisms by which aerobic training protects the heart from left ventricle (LV) hypertrophy during the onset of a fructose-induced cardiometabolic disease. METHODS Male Wistar rats were allocated into four groups (n = 8/group): Control Sedentary (C), Control Training (CT), Fructose Sedentary (F), and Fructose Training (FT). C and CT received drinking water, and the F and FT groups received d-fructose (10% water). After 2 weeks, the CT and FT rats were assigned to a treadmill training protocol at moderate intensity for eight weeks (60 min/day, 4 days/week). After ten weeks, LV morphological remodelling, cardiomyocyte apoptosis, microRNAs, and the insulin signalling pathway were investigated. RESULTS The F group had systemic cardiometabolic alterations, which were normalised by aerobic training. The LV weight increased in FT, myocardium vascularisation decreased in F, and the cardiomyocyte area increased in CT, F, and FT. Regarding the protein expressions, total-IRs decreased in the F. The p-IRs and PI3K increased in the FT. The total-AKT and p-AKT increased in all of the groups. The p-p70s6k protein was higher in the CT, and the p-ERK increased in CT and FT. MiR-126, miR-195, and cardiomyocyte apoptosis did not differ among the groups. CONCLUSION Aerobic training activates p-p70s6k and p-ERK, and during the onset of a cardiovascular disease, it can activate the IRs-PI3K-AKT pathway. This article is protected by copyright. All rights reserved.