Resistance Exercise Training Mitigates Cardiac Remodeling Induced by a High-Fat Diet in Rodents: A Systematic Review. / O Treinamento Resistido Atenua a Remodelação Cardíaca Induzida por uma Dieta Hiperlipídica em Roedores: Uma Revisão Sistemática.

BACKGROUND: Obesity is associated with the development of cardiovascular diseases and is a serious public health problem. In animal models, high-fat diet (HFD) feeding impairs cardiac structure and function and promotes oxidative stress and apoptosis. Resistance exercise training (RT), however, has been recommended as coadjutant in the treatment of cardiometabolic diseases, including obesity, because it increases energy expenditure and stimulates lipolysis. OBJECTIVE: In this systematic review, we aimed to assess the benefits of RT on the heart of rats and mice fed HFD. METHODS: Original studies were identified by searching PubMed, Scopus, and Embase databases from December 2007 to December 2022. This study was conducted in accordance with the criteria established by PRISMA and registered in PROSPERO (CRD42022369217). The risk of bias and methodological quality was evaluated by SYRCLE and CAMARADES, respectively. Eligible studies included original articles published in English that evaluated cardiac outcomes in rodents submitted to over 4 weeks of RT and controlled by a sedentary, HFD-fed control group (n = 5). RESULTS: The results showed that RT mitigates cardiac oxidative stress, inflammation, and endoplasmic reticulum stress. It also modifies the activity of structural remodeling markers, although it does not alter biometric parameters, histomorphometric parameters, or the contractile function of cardiomyocytes. CONCLUSION: Our results indicate that RT partially counteracts the HFD-induced adverse cardiac remodeling by increasing the activity of structural remodeling markers; elevating mitochondrial biogenesis; reducing oxidative stress, inflammatory markers, and endoplasmic reticulum stress; and improving hemodynamic, anthropometric, and metabolic parameters.

FUNDAMENTO: A obesidade está associada ao desenvolvimento de doenças cardiovasculares e constitui um grave problema de saúde pública. Em modelos animais, a alimentação com uma dieta hiperlipídica (DH) compromete a estrutura e a função cardíaca e promove estresse oxidativo e apoptose. O treinamento resistido (TR), entretanto, tem sido recomendado como coadjuvante no tratamento de doenças cardiometabólicas, incluindo a obesidade, porque aumenta o gasto energético e estimula a lipólise. OBJETIVO: Na presente revisão sistemática, nosso objetivo foi avaliar os benefícios do TR no coração de ratos e camundongos alimentados com DH. MÉTODOS: Foram identificados estudos originais por meio de busca nas bases de dados PubMed, Scopus e Embase de dezembro de 2007 a dezembro de 2022. O presente estudo foi conduzido de acordo com os critérios estabelecidos pelo PRISMA e registrado no PROSPERO (CRD42022369217). O risco de viés e a qualidade metodológica foram avaliados pelo SYRCLE e CAMARADES, respectivamente. Os estudos elegíveis incluíram artigos originais publicados em inglês que avaliaram desfechos cardíacos em roedores submetidos a mais de 4 semanas de TR e controlados por um grupo controle sedentário alimentado com DH (n = 5). RESULTADOS: Os resultados mostraram que o TR atenua o estresse oxidativo cardíaco, a inflamação e o estresse do retículo endoplasmático. Também modifica a atividade de marcadores de remodelamento estrutural, apesar de não alterar parâmetros biométricos, parâmetros histomorfométricos ou a função contrátil dos cardiomiócitos. CONCLUSÃO: Nossos resultados indicam que o TR parcialmente neutraliza o remodelamento cardíaco adverso induzido pela DH, aumentando a atividade dos marcadores de remodelamento estrutural; elevando a biogênese mitocondrial; reduzindo o estresse oxidativo, marcadores inflamatórios e estresse do retículo endoplasmático; e melhorando os parâmetros hemodinâmicos, antropométricos e metabólicos.

Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte Contractility in Β1 Adrenergic Receptor Knockout Mice / Treinamento Aeróbico Contínuo de Intensidade Moderada Melhora a Contratilidade do Cardiomiócito em Camundongos com Nocaute para o Receptor B1-Adrenérgico

Abstract Background: The lack of cardiac β1-adrenergic receptors (β1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF. Objective: We tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from β1 adrenergic receptor knockout (β1ARKO) mice. Methods: Four- to five-month-old male wild type (WT) and β1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and β1ARKO control (β1ARKOc) and trained (β1ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. Results: The β1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The β1ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from β1ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in β1ARKO mice. Conclusion: MCAE improves myocyte contractility in the left ventricle of β1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving β1-AR desensitization or reduction.

Resumo Fundamento: A falta de receptores β1-adrenérgicos (β1-AR) cardíacos afeta negativamente a regulação de inotropismo e lusitropismo cardíacos, levando, no longo prazo, a insuficiência cardíaca (IC). Recomenda-se exercício aeróbico contínuo de intensidade moderada (EACM) como adjuvante no tratamento de pacientes com IC. Objetivo: Testar os efeitos do EACM nas propriedades contráteis de miócitos do ventrículo esquerdo (VE) de camundongos com nocaute para o receptor β1-adrenérgico (β1ARKO). Método: Camundongos machos com 4 a 5 meses de idade, wild-type (WT) e β1ARKO foram divididos em grupos: WT controle (WTc) e treinado (WTt); e β1ARKO controle (β1ARKOc) e treinado (β1ARKOt). Os grupos treinados foram submetidos a regime de EACM (60 min/dia; 60% da velocidade máxima, 5 dias/semana) em esteira rolante, por 8 semanas. Adotou-se P ≤ 0,05 como nível de significância em todas as comparações. Resultados: Os animais β1ARKO (β1ARKOc + β1ARKOt) correram uma distância maior do que os animais WT (WTc + WTt) (p < 0,05). Os camundongos β1ARKO apresentaram maiores pesos corporal (PC), do coração (PCo) e do ventrículo esquerdo (PVE), assim como PCo/PC e PVE/PC do que os camundongos WT. Entretanto, o EACM não afetou tais parâmetros. Os miócitos do VE de camundongos β1ARKO apresentaram maiores (p < 0,05) amplitude e velocidades de contração e relaxamento do que os dos camundongos WT. Além disso, o EACM aumentou (p < 0,05) a amplitude e as velocidades de contração e relaxamento nos camundongos β1ARKO. Conclusão: O EACM melhora a contratilidade do miócito do VE de camundongos β1ARKO. Tal achado confirma o valor terapêutico desse tipo de treinamento físico para o tratamento de doenças cardíacas envolvendo dessensibilização ou redução de β1-AR.

Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte Contractility in Β1 Adrenergic Receptor Knockout Mice.

BACKGROUND: The lack of cardiac ß1-adrenergic receptors (ß1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF. OBJECTIVE: We tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from ß1 adrenergic receptor knockout (ß1ARKO) mice. METHODS: Four- to five-month-old male wild type (WT) and ß1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and ß1ARKO control (ß1ARKOc) and trained (ß1ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. RESULTS: The ß1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The ß1ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from ß1ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in ß1ARKO mice. CONCLUSION: MCAE improves myocyte contractility in the left ventricle of ß1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving ß1-AR desensitization or reduction.

Níveis distintos de Hsp72 no miocárdio de ratas em resposta aos exercícios voluntário e forçado / Different levels of Hsp72 in female rat myocardium in response to voluntary exercise and forced exercise / Niveles distintos de Hsp72 en el miocardio de ratas en respuesta a los ejercicios voluntario y forzado

FUNDAMENTO: O exercício físico promove estresse hemodinâmico. OBJETIVO: Testar se programas de treinamento com corridas voluntária e forçada induzem níveis distintos de expressão de Hsp72 no miocárdio de ratas Wistar. MÉTODOS: Ratas Wistar foram alocadas em três grupos (n = 6, cada): treinadas com corrida voluntária (TCV), treinadas com corrida forçada (TCF) e grupo controle (C). Os animais do TCV tiveram livre acesso à roda de corrida voluntária, enquanto os do TCF foram submetidos à corrida forçada em esteira (18 m/min, 0 por cento inclinação, 60 m/min, 5 dias/sem) durante oito semanas. Fragmentos dos ventrículos esquerdo (VE) e direito (VD) foram coletados para análise dos níveis de Hsp72. RESULTADOS: As ratas do grupo TCV correram, em média, 4,87 km, e as do TCF, 4,88 km por semana. Os animais dos grupos TCV e TCF ganharam menos peso (p < 0,05) que os do grupo C (81,67 ± 11,95 g vs 81,17 ± 10,18 g vs 111,50 ± 2,26 g, respectivamente). O peso relativo do coração não foi diferente (p > 0,05) entre os grupos TCV, TCF e C (4,54 ± 0,79 mg/g vs 4,94 ± 0,89 mg/g vs 4,34 ± 0,87 mg/g, respectivamente). Ratas treinadas com corrida forçada apresentaram níveis de Hsp72 maiores (p < 0,05) que as que correram voluntariamente, no VE (287,45 ± 35,86 por cento vs 135,59 ± 5,10 por cento, respectivamente) e no VD (241,31 ± 25,83 por cento vs 137,91 ± 45,20 por cento, respectivamente). CONCLUSÃO: Os programas de treinamento com corrida voluntária e forçada induziram níveis distintos de expressão de Hsp72 no miocárdio de ratas Wistar.

BACKGROUND: Physical exercise induces hemodynamic stress. OBJECTIVE: To evaluate if voluntary running and forced running induced different levels of stress protein (Hsp72) in the myocardium of female Wistar rats. METHODS: Female rats were randomly assigned to the following groups: forced treadmill running group (FR; n= 6), voluntary running group (VR; n=6) and control group (C; n=6). VR group animals had free access to running wheels, and those from FR group underwent a running program on a treadmill (18 m/min, 60 min/day, 5 days/wk) for 8 weeks. Left ventricle (LV) and right ventricle (RV) fragments were collected at sacrifice, and the relative immunoblot contents of stress protein (Hsp72) were determined. RESULTS: VR animals ran on average 4.87 km/wk, and FR rats ran 4.88 km/wk. Animals from VR and FR groups had less body weight gain (p<0.05) than those from C group (81.67 ± 11.95g vs 81.17 ± 10.18g vs 111.50 ± 2.26g, respectively). Heart weight/body weight ratio was not significantly different (p>0.05) among VR, FR and C groups (4.54 ± 0.79 mg/g vs 4.94 ± 0.89 mg/g vs 4.34 ± 0.87 mg/g, respectively). FR group animals had levels of Hsp72 (p<0.05) higher than those from VR, both in LV (287.45 ± 35.86 percent vs 135.59 ± 5.10 percent, respectively) and RV (241.31 ± 25.83 percent vs 137.91 ± 45.20 percent, respectively). CONCLUSION: Voluntary running and forced running induced different levels of Hsp72 in the myocardium of female Wistar rats.

FUNDAMENTO: El ejercicio físico promueve estrés hemodinámico. OBJETIVO: Probar si programas de entrenamiento con carreras voluntaria y forzada inducen niveles distintos de expresión de Hsp72 en el miocardio de ratas hembra Wistar. MÉTODOS: Ratas hembra Wistar fueron distribuidas en tres grupos (n = 6, cada uno): entrenadas con carrera voluntaria (ECV), entrenadas con carrera forzada (ECF) y grupo control (C). Los animales del ECV tuvieron libre acceso a la rueda de carrera voluntaria, mientras que los del ECF fueron sometidos a carrera forzada en cinta sin fin (18 m/min, 0 por ciento inclinación, 60 m/min, 5 días/sem) durante ocho semanas. Fragmentos de los ventrículos izquierdo (VI) y derecho (VD) se recolectaron para análisis de los niveles de Hsp72. RESULTADOS: Las ratas del grupo ECV corrieron, en promedio 4,87 km, y las del ECF, 4,88 km por semana. Los animales de los grupos ECV y ECF ganaron menos peso (p<0,05) que los del grupo C (81,67 ± 11,95 g vs. 81,17 ± 10,18 g vs. 111,50 ± 2,26 g, respectivamente). El peso relativo del corazón no fue diferente (p>0,05) entre los grupos ECV, ECF y C (4,54 ± 0,79 mg/g vs. 4,94 ± 0,89 mg/g vs. 4,34 ± 0,87 mg/g, respectivamente). Las ratas entrenadas con carrera presentaron niveles de Hsp72 mayores (p<0,05) que las que corrieron voluntariamente, en el VI (287,45 ± 35,86 por ciento vs. 135,59 ± 5,10 por ciento, respectivamente) y en el VD (241,31 ± 25,83 por ciento vs. 137,91 ± 45,20 por ciento, respectivamente). CONCLUSIÓN: Los programas de entrenamiento con carreras voluntaria y forzada inducen niveles distintos de expresión de Hsp72 en el miocardio de ratas Wistar.

Different levels of Hsp72 in female rat myocardium in response to voluntary exercise and forced exercise.

BACKGROUND: Physical exercise induces hemodynamic stress. OBJECTIVE: To evaluate if voluntary running and forced running induced different levels of stress protein (Hsp72) in the myocardium of female Wistar rats. METHODS: Female rats were randomly assigned to the following groups: forced treadmill running group (FR; n= 6), voluntary running group (VR; n=6) and control group (C; n=6). VR group animals had free access to running wheels, and those from FR group underwent a running program on a treadmill (18 m/min, 60 min/day, 5 days/wk) for 8 weeks. Left ventricle (LV) and right ventricle (RV) fragments were collected at sacrifice, and the relative immunoblot contents of stress protein (Hsp72) were determined. RESULTS: VR animals ran on average 4.87 km/wk, and FR rats ran 4.88 km/wk. Animals from VR and FR groups had less body weight gain (p<0.05) than those from C group (81.67 +/- 11.95g vs 81.17 +/- 10.18g vs 111.50 +/- 2.26g, respectively). Heart weight/body weight ratio was not significantly different (p>0.05) among VR, FR and C groups (4.54 +/- 0.79 mg/g vs 4.94 +/- 0.89 mg/g vs 4.34 +/- 0.87 mg/g, respectively). FR group animals had levels of Hsp72 (p<0.05) higher than those from VR, both in LV (287.45 +/- 35.86 % vs 135.59 +/- 5.10 %, respectively) and RV (241.31 +/- 25.83 % vs 137.91 +/- 45.20 %, respectively). CONCLUSION: Voluntary running and forced running induced different levels of Hsp72 in the myocardium of female Wistar rats.