ABC | Volume 115, Nº2, August 2020

Original Article Intermittent Fasting Attenuates Exercise Training-Induced Cardiac Remodeling Priscilla Gois Basilio, 1 Ana Priscila Cayres de Oliveira, 1 Ana Carolini Ferreira de Castro, 1 Marianna Rabelo de Carvalho, 1 A lessandro Moura Zagatto, 2 P aula Felippe Martinez, 1 Marina Politi Okoshi, 3 Katashi Okoshi, 2 Gabriel Elias Ota, 1 Filipe Abdalla dos Reis, 4 Silvio Assis de Oliveira-Junior 1 Laboratory of Striated Muscle Study (LEME/ INISA), Federal University of Mato Grosso do Sul, 1 Campo Grande, MS - Brazil Department of Physical Education, Laboratory of Physiology and Sport Performance (LAFIDE), School of Sciences, São Paulo State University, UNESP 2 , Bauru, SP - Brazil Botucatu Medical School, São Paulo State University, UNESP, 3 Botucatu, SP - Brazil Centro Universitário Anhanguera de Campo Grande, 4 Campo Grande, MS – Brazil Mailing Adress: Silvio Assis de Oliveira-Junior • Universidade Federal de Mato Grosso do Sul (UFMS), Instituto Integrado de Saúde, Laboratório de Estudo do Músculo Estriado (LEME/INISA) - Av. Costa e Silva, s/n. Postal Code 79070-900, Cidade Universitária, Campo Grande, MS – Brazil E-mail: oliveirajr.ufms@gmail.com, silvio.oliveira-jr@ufms.br Manuscript received May 29, 2019, revised manuscript August 14, 2019, accepted August 14, 2019 DOI: https://doi.org/10.36660/abc.20190349 Abstract Background: The effects of non-pharmacological interventions such as calorie restriction and exercise training on health and prevention of cardiovascular diseases have been investigated in clinical and experimental studies. Objective: To analyze the influence of intermittent fasting and exercise training on functional fitness, glycemia and cardiac remodeling. Methods: Wistar rats (n=60) were randomly divided into four groups: control, exercise training (ET), intermittent fasting (IF) and exercise training plus intermittent fasting (ETI). Over 12 weeks, control and ET animals were fed daily a standard commercial diet ad libitum , while IF and ETI animals were fed every other day. In addition, the ET and ETI groups were submitted to a running protocol on a treadmill. After this period, functional fitness, nutritional parameters and blood glucose levels were analyzed. In addition to heart morphology, myocardial protein expression of extracellular signal- regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was assessed by Western-blot. The results were analyzed using two-way ANOVA and Student-Newman-Keuls test. The level of significance considered was 5%. Results: Exercise training increased functional fitness in the ET and ETI groups and promoted cardiac fibrosis. The combination of intermittent fasting and exercise training resulted in a smaller area under the blood glucose curve and reduced cardiomyocyte cross-sectional area and interstitial collagen fraction in the ETI group compared to ET. ERK and JNK expression levels were similar among groups (p>0.05). Conclusions: Intermittent fasting is associated with improved glucose tolerance and attenuates cardiac remodeling induced by exercise training (Arq Bras Cardiol. 2020; 115(2):184-193) Keywords: Diet; Calorie Restriction; Exercise; Running; Ventricular Remodeling; Glucose; Health Promotion. Introduction Classically, calorie restriction is a popular intervention for health improvement, promoting multiple functional benefits and increasing human longevity. 1-4 However, experimental studies have reported controversial changes in cardiovascular parameters in response to calorie restriction, which was found to be associated with contractile dysfunction and myocardial morphological damage. 5-8 Some researchers demonstrated that calorie restriction promoted ultrastructural injuries to cardiac myofibrils and changes in intracellular calcium handling; these responses were related to β -adrenergic system disorders and myocardial contractile dysfunction. 5,7,9 Other morphological changes included ventricular chamber dilation, cardiomyocyte necrosis, interstitial fibrosis and mitochondrial swelling. 10-12 On the other hand, intermittent fasting (IF) intervention, a model of calorie restriction, was associated with few morphological changes and did not promote myocardial dysfunction after a period of 12 weeks compared to 50% calorie restriction. 11 In this dietary approach, food is available ad libitum at intervals alternating with fasting periods, each lasting 12 to 24 hours. 3,4 However, the effects of IF on the heart remain unknown. At the molecular level, the association of mitogen-activated protein kinases (MAPKs), important mediators of cardiac remodeling, 13 has not been studied in calorie restriction models. MAPKs include three main subtypes, extracellular signal-regulated kinase (ERK), c-Jun N-terminal 184