Kindlovits Raquel, Bertoldi Julia Maria Cabral Relvas Jacome, Rocha Helena Naly Miguens, Bento-Bernardes Thais, Gomes João Lucas Penteado, de Oliveira Edilamar Menezes, Muniz Ingrid Cristina, Pereira Juliana Frota, Fernandes-Santos Caroline, Rocha Natália Galito, Nóbrega Antonio Claudio Lucas da, Medeiros Renata Frauches
Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
National Institute for Science and Technology - INCT Physical (In)activity and Exercise, CNPq -, Niterói, Rio de Janeiro, Brazil.
Exp Physiol. 2021 May;106(5):1224-1234. doi: 10.1113/EP088845. Epub 2021 Mar 18.
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 is the main finding and its importance? At the onset of cardiovascular disease, aerobic training activates the p-p70S6K, ERK and IRβ-PI3K-AKT pathways, without changing the miR-126 and miR-195 levels, thereby providing evidence that aerobic training modulates the insulin signalling pathway. These data contribute to the understanding of the molecular cardiac changes that are associated with physiological left ventricular hypertrophy during the development of a cardiovascular disease.
During the onset of cardiovascular disease (CVD), disturbances in myocardial vascularization, cell proliferation and protein expression are observed. Aerobic training prevents CVD, but the underlying mechanisms behind left ventricle (LV) hypertrophy are not fully elucidated. The aim of this study was to investigate the mechanisms by which aerobic training protects the heart from LV hypertrophy during the onset of fructose-induced cardiometabolic disease. Male Wistar rats were allocated to four groups (n = 8/group): control sedentary (C), control training (CT), fructose sedentary (F) and fructose training (FT). The C and CT groups received drinking water, and the F and FT groups received d-fructose (10% in water). After 2 weeks, the CT and FT rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min/day, 4 days/week). After 10 weeks, LV morphological remodelling, cardiomyocyte apoptosis, microRNAs and the insulin signalling pathway were investigated. The F group had systemic cardiometabolic alterations, which were normalised by aerobic training. The LV weight increased in the FT group, myocardium vascularisation decreased in the F group, and the cardiomyocyte area increased in the CT, F and FT groups. Regarding protein expression, total insulin receptor β-subunit (IRβ) decreased in the F group; phospho (p)-IRβ and phosphoinositide 3-kinase (PI3K) increased in the FT group; total-AKT and p-AKT increased in all of the groups; p-p70S6 kinase (p70S6K) protein was higher in the CT group; and p-extracellular signal-regulated kinase (ERK) increased in the CT and FT groups. MiR-126, miR-195 and cardiomyocyte apoptosis did not differ among the groups. Aerobic training activates p-p70S6K and p-ERK, and during the onset of a CVD, it can activate the IRβ-PI3K-AKT pathway.
本研究的核心问题是什么？在Wistar大鼠高果糖诱导的心脏代谢疾病进展过程中，有氧训练心脏保护作用的潜在机制是什么？主要发现及其重要性是什么？在心血管疾病发作时，有氧训练可激活p-p70S6K、ERK和IRβ-PI3K-AKT信号通路，而不改变miR-126和miR-195的水平，从而为有氧训练调节胰岛素信号通路提供了证据。这些数据有助于理解在心血管疾病发展过程中与生理性左心室肥厚相关的分子心脏变化。
在心血管疾病（CVD）发作期间，可观察到心肌血管生成、细胞增殖和蛋白质表达的紊乱。有氧训练可预防CVD，但左心室（LV）肥厚背后的潜在机制尚未完全阐明。本研究的目的是探讨有氧训练在果糖诱导的心脏代谢疾病发作期间保护心脏免受LV肥厚的机制。将雄性Wistar大鼠分为四组（每组n = 8）：对照组久坐不动（C）、对照组训练（CT）、果糖组久坐不动（F）和果糖组训练（FT）。C组和CT组给予饮用水，F组和FT组给予d-果糖（水中10%）。2周后，将CT组和FT组大鼠分配到中等强度的跑步机训练方案中，持续8周（每天60分钟，每周4天）。10周后，研究LV形态重塑、心肌细胞凋亡、微小RNA和胰岛素信号通路。F组出现全身性心脏代谢改变，有氧训练使其恢复正常。FT组LV重量增加，F组心肌血管生成减少，CT组、F组和FT组心肌细胞面积增加。关于蛋白质表达，F组总胰岛素受体β亚基（IRβ）减少；FT组磷酸化（p）-IRβ和磷酸肌醇3激酶（PI3K）增加；所有组总AKT和p-AKT均增加；CT组p-p70S6激酶（p70S6K）蛋白较高；CT组和FT组p-细胞外信号调节激酶（ERK）增加。各组间miR-126、miR-195和心肌细胞凋亡无差异。有氧训练可激活p-p70S6K和p-ERK，在CVD发作期间，它可激活IRβ-PI3K-AKT信号通路。
