A High-Fat Diet Induces Cardiac Damage in Obesity-Resistant Rodents with Reduction in Metabolic Health.

BACKGROUND/AIMS: Obesity resistance is associated with the complex interaction of stringent and environmental factors that confer the ability to resist mass gain and body fat deposition, even when eating high-calorie diets. Considering that there are numerous gaps in the literature on the metabolic processes that explain Obesity resistance, specifically in relation to oxidative stress, the purpose of the study was to investigate whether obesity-resistant (OR) rats develop elevated reactive oxygen species in cardiac tissue. METHODS: Wistar rats were initially randomized into two groups: a standard diet (SD) and a high-fat diet (HFD) group. The SD and HFD groups were further divided into control (C), OR, and obese prone (OP) subgroups based on body weight. This criterion consisted of organizing the animals in each group in ascending order according to body weight (BW), and the cutoff point was identified in the animals by terciles: 1) lower BW; 2) intermediate BW; and 3) higher BW. Rats were sacrificed on the 14th week, and serum and organs were collected. Nutritional assessment, food profiles, histological analysis, comorbidities, and cardiovascular characteristics were determined. RESULTS: BW showed a significant difference between the standard diet and high-fat diet groups in the 4th week of the experimental protocol, characterizing obesity. In the 4th week, after the characterization of Obesity resistance, there was a significant difference in BW between groups C, OP, and OR. The OP and OR groups showed a significant increase in caloric intake in relation to the C group. The OP group showed a significant increase in final BW, retroperitoneal fat pad mass, sum of corporal fat deposits and reactive oxygen species, in relation to groups C and OR. The area under the glycemic curve, insulin resistance index and basal glucose were elevated in the OP group in relation to the C. OP also promoted an increase in HOMA-IR when compared with C. OR rats showed a non-significant increase in insulin and HOMA-IR in OR vs. C (p = ~0.1), but no significant differences were observed between OP vs. OR for these parameters, suggesting that both groups suffered from decreased metabolic health. Total cardiac mass, left ventricular cross-sectional area, and cholesterol levels were significantly elevated in the OP and OR groups compared with the C group. CONCLUSION: A high-fat diet induces cardiac damage in obesity-resistant rodents with reduction in metabolic health.

Aerobic Exercise Training Improves Calcium Handling and Cardiac Function in Rats with Heart Failure Resulting from Aortic Stenosis.

Aerobic exercise training (AET) has been used to manage heart disease. AET may totally or partially restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis (AoS). This study aimed to evaluate the impact of AET on Ca2+ handling and cardiac function in rats with heart failure due to AoS. Wistar rats were distributed into two groups: control (Sham; n = 61) and aortic stenosis (AoS; n = 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. The cardiac function was analyzed by echocardiogram, isolated papillary muscles, and isolated cardiomyocytes. During assays of isolated papillary muscles and isolated cardiomyocytes, the Ca2+ concentrations were evaluated. The expression of regulatory proteins for diastolic Ca2+ was assessed via Western Blot. AET attenuated the diastolic dysfunction and improved the systolic function. AoS-ET animals presented an enhanced response to post-rest contraction and SERCA2a and L-type Ca2+ channel blockage compared to the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented an alteration in the protein expression of SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity and myofilament responsiveness to Ca2+ and improved the cellular Ca2+ influx mechanism, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with AoS and heart failure.

High-fat, high-sucrose, and combined high-fat/high-sucrose diets effects in oxidative stress and inflammation in male rats under presence or absence of obesity.

The study examines the influence of three types of hypercaloric diets on metabolic parameters, inflammatory markers, and oxidative stress in experimental model. Male Wistar rats (n = 40) were randomized in control (C), high-sucrose (HS), high-fat (HF), and high-fat with sucrose (HFHS) for 20 weeks. Nutritional, metabolic, hormonal, and biochemical profiles, as well as histological analysis of adipose and hepatic tissues were performed. Inflammation and oxidative stress were determined. HF model caused obesity and comorbidities as glucose intolerance and arterial hypertension. In relation to hormonal and biochemical parameters, there was no significant difference between the groups. All groups showed increased deposition of fat droplets in the hepatic tissue, even though adipocyte areas were similar. Biomarkers of oxidative stress in serum and adipose tissues were similar among the groups. HF model was effective in triggering associated obesity and comorbidities in male rats, but all hypercaloric diets were unable to promote oxidative stress and inflammation.

Associação entre marcadores inflamatórios e o padrão locomotor durante a ultrapassagem de obstáculos em idosos / Association between inflammatory markers and locomotor pattern during obstacle avoidance in older adults

Resumo Objetivo investigar a associação dos biomarcadores inflamatórios na tarefa de ultrapassagem de obstáculos com diferentes níveis de complexidade manipulados pela característica do obstáculo (sólido e frágil) em idosos. Método 17 idosos (≥60 anos) foram avaliados em dois momentos: 1) Análise do padrão locomotor durante a ultrapassagem de obstáculo em duas condições (sólido e frágil). As variáveis estudadas, para membros de abordagem e suporte foram: velocidade, comprimento, largura e duração da passada, distância horizontal pé-obstáculo, distância horizontal obstáculo-pé, distância vertical pé-obstáculo e Máxima elevação do pé. 2) A análise dos biomarcadores interleucina 6 (IL-6) e proteína C Reativa (PCR) foi realizada por meio de coleta de sanguínea. A análise de regressão linear múltipla foi realizada para verificar associação entre o padrão locomotor e os biomarcadores inflamatórios (IL-6 e PCR) com nível de significância de p≤0,05. Resultados A análise de regressão mostrou que a Interleucina 6 apresentou associação com as seguintes variáveis: 1) largura da passada na condição obstáculo sólido, 2) máxima elevação do pé (membro de suporte) para ultrapassagem do obstáculo frágil, 3) distância horizontal pé-obstáculo (membro de abordagem) na condição de obstáculo sólido, 4) máxima elevação do pé (membro de abordagem) para ultrapassagem do obstáculo frágil, 5) máxima elevação do pé (membro de abordagem) para ultrapassagem do obstáculo sólido. A PCR apresentou associação com a variável Distância Horizontal Pé-Obstáculo (membro de abordagem) apenas para a condição de obstáculo frágil. Conclusão Os biomarcadores inflamatórios apresentam uma associação com o comportamento locomotor em idosos, independente da condição de fragilidade do obstáculo.

Abstract Objective to investigate the association of inflammatory biomarkers on the locomotor pattern during obstacle avoidance with different levels of complexity manipulated by the characteristic of the obstacle (solid and fragile) in older adults. Method 17 older adults (≥60 years old) were evaluated in two moments: 1) Analysis of the locomotor pattern during obstacle crossing in two conditions (solid and fragile). The variables studied for trailing and leading limbs were: speed, length, width and duration of the stride, horizontal foot-obstacle distance, horizontal obstacle-foot distance, vertical foot-obstacle distance and Maximum foot elevation. 2) Blood collection, for analysis of the inflammatory biomarkers Interleukin 6 (IL6) and C-Reactive Protein (CRP). Multiple linear regression analysis was performed to verify association between locomotor pattern and inflammatory biomarkers (IL6 and CRP) with a significance level of p≤0.05. Results The regression analysis showed that Interleukin 6 was associated with the following variables: 1) stride width in the solid obstacle condition, 2) maximum foot elevation (leading limb) to avoidance the fragile obstacle, 3) horizontal foot-obstacle distance (trailing limb) in solid obstacle condition, 4) maximum foot elevation (trailing limb) to avoidance the fragile obstacle, 5) maximum foot elevation (trailing limb) to avoidance the solid obstacle. C-Reactive Protein was associated with the horizontal foot-obstacle distance (trailing limb) only for the fragile obstacle condition. Conclusion Inflammatory biomarkers are associated with the locomotor pattern in older adults, regardless of the fragility of the obstacle.

Hibiscus increases functional capacity and the anti-obesity effect in trained obese rats / El hibiscus aumenta la capacidad funcional y el efecto antiobesidad en ratas obesas entrenadas / O hibiscus aumenta a capacidade funcional e o efeito antiobesidade em ratos obesos treinados

ABSTRACT Introduction Hibiscus sabdariffa (Hs) has been widely used for weight loss and in the fight against obesity-associated comorbidities. Objective To evaluate the effects of Hs and physical training on the functional capacity of normal-weight and obese rats. Methods Wistar rats were distributed into eight experimental groups: control (C, n = 8) , Hibiscus Sabdariffa (Hs, n = 8), high-intensity interval training (IT, n = 8), high-intensity interval training + Hibiscus Sabdariffa (ITHs, n = 8), obese (O, n = 8), obese + continuous aerobic training (OAT, n = 8), obese + Hibiscus Sabdariffa (OHs, n = 8), , and obese + continuous aerobic training + Hibiscus Sabdariffa (OATHs, n = 8). Hibiscus Sabdariffa extract was administered for 60 days in a dose of 150 mg/kg of body weight. The maximum progressive effort test (MPET) was performed on a treadmill at the beginning and end of the study. The variables analyzed were maximum speed Vmáx time, and distance covered. Lactate was measured immediately after the MPET. Functional capacity was evaluated by the distance/adiposity index. The ANOVA with Bonferroni post hoc and Pearson's correlation tests were used at a 5% significance level. Results After both types of training, moderate-intensity continuous and high-intensity interval performed on the treadmill, final body weight, weight gain, and the adiposity index decreased, and Vmax, time, and distance covered in the MPET increased, in addition to an improvement in functional capacity. Hs supplementation reduced the adiposity index in normal-weight and obese rats. Hs associated with aerobic training reduced final body weight and increased functional capacity. Conclusion Hs supplementation promoted a reduction in the adiposity index in normal-weight and obese rats and an increase in the functional capacity of trained obese rats. Level of Evidence III; Therapeutic Studies - Outcome Investigation. Case study - control.

RESUMEN Introducción El Hibiscus Sabdariffa (Hs) ha sido ampliamente utilizado para promover la pérdida de peso y tratar las comorbilidades asociadas a la obesidad. Objetivos Evaluar los efectos del Hs y el entrenamiento físico sobre la capacidad funcional de ratas eutróficas y obesas. Métodos Se distribuyeron ratas Wistar en ocho grupos experimentales: Control (C, n=8), Hibiscus Sabdariffa (Hs, n=8), , entrenamiento de intervalos de alta intensidad (EI, n=8)), entrenamiento de intervalos de alta intensidad + Hibiscus Sabdariffa (EIHs, n=8), obeso (O, n=8)), obeso + entrenamiento continuo aeróbico (OEA, n=8), obeso + Hibiscus Sabdariffa (OHs, n=8), obeso + entrenamiento continuo aeróbico + Hibiscus Sabdariffa (OEAHs, n=8). Se administró extracto de Hibiscus Sabdariffa durante 60 días a una dosis de 150 mg / kg de peso corporal. Se realizó una prueba de esfuerzo progresivo máximo (PEPM) en una cinta rodante al principio y al final del estudio. Las variables analizadas fueron: velocidad máxima Vmáx, tiempo y distancia recorrida. El nivel de lactato se midió inmediatamente después de la PEPM. La capacidad funcional se evaluó mediante el índice de distancia / adiposidad. Se empleó el método ANOVA con post hoc de Bonferroni y las pruebas de correlación de Pearson, a un nivel de significancia del 5%. Resultados Después de ambos tipos de entrenamiento, el entrenamiento continuo a intensidad moderada y el entrenamiento de intervalos de alta intensidad realizados en cinta rodante, las ratas presentaron disminución del peso corporal final, aumento de peso e índice de adiposidad, así como aumentaron la Vmax, el tiempo y la distancia recorrida en la PEPM, y mejoraron la capacidad funcional. La suplementación con Hs disminuyó el índice de adiposidad en ratas eutróficas y obesas. El Hibiscus asociado al entrenamiento aeróbico redujo el peso corporal final y aumentó la capacidad funcional. Conclusión La suplementación con Hs redujo el índice de adiposidad en ratas eutróficas y obesas y aumentó la capacidad funcional de ratas obesas entrenadas. Nivel de Evidencia III; Estudios Terapéuticos - Investigación de Resultados. Estudio de caso - control.

RESUMO Introdução O Hibiscus Sabdariffa (Hs) tem sido amplamente utilizado para emagrecimento e no combate às comorbidades associadas à obesidade. Objetivos Avaliar os efeitos do Hs e do treinamento físico sobre a capacidade funcional de ratos eutróficos e obesos. Métodos Ratos Wistar foram distribuídos em oito grupos experimentais: Controle (C, n = 8), Hibiscus Sabdariffa (Hs, n = 8), treinamento intervalado de alta intensidade (TI, n = 8), treinamento intervalado de alta intensidade + Hibiscus Sabdariffa (TIHs, n = 8), obeso (O, n = 8), obeso + treinamento contínuo aeróbico (OTA, n = 8), obeso+ Hibiscus Sabdariffa (OHs, n = 8), obeso + treinamento contínuo aeróbico + Hibiscus Sabdariffa (OTAHs, n = 8). O extrato de Hibiscus Sabdariffa foi administrado por 60 dias na dose de 150 mg/kg de peso corporal. Foi realizado teste de esforço progressivo máximo (TEPM) em esteira no início e no final do estudo. As variáveis analisadas foram: velocidade máxima (Vmáx), tempo e distância percorrida. O lactato foi mensurado imediatamente depois do TEMP. A capacidade funcional foi avaliada pela distância/índice de adiposidade. Empregou-se ANOVA com post hoc de Bonferroni e correlação de Pearson, adotando-se o nível de significância de 5%. Resultados Depois de ambos os tipos de treinamento, o contínuo em moderada intensidade e o intervalado de alta intensidade realizados em esteira, reduziram o peso corporal final, o ganho de peso e o índice de adiposidade, bem como aumentaram a Vmáx, tempo e distância percorrida no TEPM, além de melhora da capacidade funcional. A suplementação de Hs diminuiu o índice de adiposidade nos ratos eutróficos e obesos. O Hs associado ao treinamento aeróbico reduziu o peso corporal final e aumentou a capacidade funcional. Conclusão A suplementação de Hs promoveu redução no índice de adiposidade em ratos eutróficos e obesos e aumentou a capacidade funcional de ratos obesos treinados. Nível de evidência III; Estudos Terapêuticos - Investigação de Resultados. Estudo caso controle .

Resistance to obesity prevents obesity development without increasing spontaneous physical activity and not directly related to greater metabolic and oxidative capacity.

There are evidence that obese-resistant animals are more physically active, due to a higher rate of lipid oxidation. Efficiency in such pathways can favor greater spontaneous physical activity and, consequently, less body fat deposition. The aim of study was characterizing the nutritional profile and spontaneous physical activity in the condition of Resistance to Obesity (OR). Wistar rats were randomized into standard diet (SD; n = 50) and high-fat diet (HFD; n = 50) groups, after obesity induction, were redistributed into Control (C), False-control (FC), Propensity to obesity (OP) and OR, and then spontaneous physical activity was evaluated. Analyzed parameters: body mass (BM), epididymal (EF), retroperitoneal (RF), visceral (VF) and respective summations (∑), adiposity index (AI), nutritional, morphological, biochemical and metabolic parameters and protein quantification. The comparison of the groups was performed by ANOVA one or two factors, with 5% significance adopted. OP and FC presented high final MC values compared to C and OR. OR had lower EF, RF, VF, ∑ and IA compared to OP. OR had similar values to C and higher HDL than FC and OP. In GTT, OR and C presented similar values and both were lower than OP in the 30 minutes. OP promoted higher values than C for glycemic AUC. OR had higher PPARγ content than C and OP, as well as levels similar to C for leptin and insulin. Spontaneous physical activity did not differ between groups. The results were not enough to show that OR animals have greater lipid oxidative capacity, as well as greater spontaneous physical activity.

The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis. / Cenário Disfuncional dos Principais Componentes Responsáveis pelo Equilíbrio do Trânsito de Cálcio Miocárdico na Insuficiência Cardíaca Induzida por Estenose Aórtica.

BACKGROUND: Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling. OBJECTIVE: To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis. METHODS: Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05. RESULTS: Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger. CONCLUSION: Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.

FUNDAMENTO: O remodelamento cardíaco patológico se caracteriza por disfunção diastólica e sistólica, levando à insuficiência cardíaca. Neste contexto, o cenário disfuncional do trânsito de cálcio miocárdico (Ca2+) tem sido pouco estudado. Um modelo experimental de estenose aórtica tem sido extensamente utilizado para aprimorar os conhecimentos sobre os principais mecanismos do remodelamento patológico cardíaco. OBJETIVO: Entender o processo disfuncional dos principais componentes responsáveis pelo equilíbrio do cálcio miocárdico e sua influência sobre a função cardíaca na insuficiência cardíaca induzida pela estenose aórtica. MÉTODOS: Ratos Wistar de 21 dias de idade foram distribuídos em dois grupos: controle (placebo; n=28) e estenose aórtica (EaO; n=18). A função cardíaca foi analisada com o ecocardiograma, músculo papilar isolado e cardiomiócitos isolados. No ensaio do músculo papilar, SERCA2a e a atividade do canal de Ca2+ do tipo L foram avaliados. O ensaio de cardiomiócitos isolados avaliou o trânsito de cálcio. A expressão proteica da proteínas do trânsito de cálcio foi analisada com o western blot. Os resultados foram estatisticamente significativos quando p <0,05. RESULTADOS: Os músculos papilares e cardiomiócitos dos corações no grupo EaO demonstraram falhas mecânicas. Os ratos com EaO apresentaram menor tempo de pico do Ca2+, menor sensibilidade das miofibrilas do Ca2+, prejuízos nos processos de entrada e recaptura de cálcio pelo retículo sarcoplasmático, bem como disfunção no canal de cálcio do tipo L (CCTL). Além disso, os animais com EaO apresentaram maior expressão de SERCA2a, CCTL e trocador de Na+/Ca2+. CONCLUSÃO: Insuficiência cardíaca sistólica e diastólica devido à estenose aórtica supravalvular acarretou comprometimento da entrada de Ca2+ celular e inibição da recaptura de cálcio pelo retículo sarcoplasmático devido à disfunção no CCTL e SERCA2a, assim como mudanças no trânsito de cálcio e na expressão das principais proteínas responsáveis pela homeostase de Ca2+ celular.

Physical exercise attenuates stress-induced hypertension in rats but not the impairments on the myocardial mechanics.

BACKGROUND: Acute and chronic stresses have become a health problem in the contemporary society, and prolonged exposure to stressful events are related to the pathogenesis of cardiovascular diseases. Physical exercise is a well-recognized effective nonpharmacological therapy for cardiovascular diseases and stress-induced injuries. Thus, this study evaluated the effect of exercise on the cardiac remodelling of chronically stressed rats. METHODS AND RESULTS: Wistar adult rats were used (n = 10 each group) and chronic stress protocol consisted of restricting movement in individual rodent restrainers (60 min, 5 days/week, 12 weeks); and exercise consisted of swimming sessions in a pool (60 min, 5 days/week, 12 weeks). During protocol, blood pressure was measured in conscious rats, and at the end cardiac morphology/function was assessed. Animals exposed to stress exhibited continuous rise in blood pressure from the sixth week, but exercise attenuated it. Similarly, restrained rats increased serum corticosterone compared with nonstressed rats, but exercise also prevented it. No changes were found in cardiac mass, but chronic stress not only impaired the steady state contractions of the cardiac muscle, but also reduced inotropic responses to stretching, increasing calcium and beta-adrenergic receptor stimulation. Despite this, exercise was unable to prevent these functional impairments induced by stress, and instead, the association of stress and physical exercise worsened myocardial compliance. CONCLUSION: Despite the known benefits to the cardiovascular system, our results indicate that aerobic swimming exercise for 12 weeks reduced blood pressure but did not impede the chronic stress-induced myocardial damages in rats.

Cenário Disfuncional dos Principais Componentes Responsáveis pelo Equilíbrio do Trânsito de Cálcio Miocárdico na Insuficiência Cardíaca Induzida por Estenose Aórtica / The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis

Resumo Fundamento O remodelamento cardíaco patológico se caracteriza por disfunção diastólica e sistólica, levando à insuficiência cardíaca. Neste contexto, o cenário disfuncional do trânsito de cálcio miocárdico (Ca2+) tem sido pouco estudado. Um modelo experimental de estenose aórtica tem sido extensamente utilizado para aprimorar os conhecimentos sobre os principais mecanismos do remodelamento patológico cardíaco. Objetivo Entender o processo disfuncional dos principais componentes responsáveis pelo equilíbrio do cálcio miocárdico e sua influência sobre a função cardíaca na insuficiência cardíaca induzida pela estenose aórtica. Métodos Ratos Wistar de 21 dias de idade foram distribuídos em dois grupos: controle (placebo; n=28) e estenose aórtica (EaO; n=18). A função cardíaca foi analisada com o ecocardiograma, músculo papilar isolado e cardiomiócitos isolados. No ensaio do músculo papilar, SERCA2a e a atividade do canal de Ca2+ do tipo L foram avaliados. O ensaio de cardiomiócitos isolados avaliou o trânsito de cálcio. A expressão proteica da proteínas do trânsito de cálcio foi analisada com o western blot. Os resultados foram estatisticamente significativos quando p <0,05. Resultados Os músculos papilares e cardiomiócitos dos corações no grupo EaO demonstraram falhas mecânicas. Os ratos com EaO apresentaram menor tempo de pico do Ca2+, menor sensibilidade das miofibrilas do Ca2+, prejuízos nos processos de entrada e recaptura de cálcio pelo retículo sarcoplasmático, bem como disfunção no canal de cálcio do tipo L (CCTL). Além disso, os animais com EaO apresentaram maior expressão de SERCA2a, CCTL e trocador de Na+/Ca2+. Conclusão Insuficiência cardíaca sistólica e diastólica devido à estenose aórtica supravalvular acarretou comprometimento da entrada de Ca2+ celular e inibição da recaptura de cálcio pelo retículo sarcoplasmático devido à disfunção no CCTL e SERCA2a, assim como mudanças no trânsito de cálcio e na expressão das principais proteínas responsáveis pela homeostase de Ca2+ celular.

Abstract Background Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling. Objective To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis. Methods Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05. Results Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger. Conclusion Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.

High-Fat and Combined High-Fat and Sucrose Diets Promote Cardiac Oxidative Stress Independent of Nox2 Redox Regulation and Obesity in Rats.

BACKGROUND/AIMS: Oxidative stress is associated with cardiometabolic alterations, and the involvement of excess glucose and fatty acids has been demonstrated in this process. Thus, the aim of this study was to investigate the effects of different hypercaloric diets on cardiac oxidative stress. METHODS: Wistar rats were randomized into four groups: control (C), high-sucrose (HS), high-fat (HF), and high-fat with sucrose (HFS). Nutritional assessment, food profiles, histological analysis, comorbidities, and cardiovascular characteristics were determined. Cardiac oxidative stress was analyzed by malondialdehyde (MDA) and carbonylated proteins, and the cardiac protein expression levels of type 1 angiotensin receptor (AT-1), nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2), superoxide dismutase (SOD 1 e 2), glutathione peroxidase (GPX), and catalase (CAT) were determined by western blot. RESULTS: The HF group showed an increase in adiposity; however, it did not present adipocyte hypertrophy and comorbidities. Cardiac MDA and carbonylated protein levels were higher in the HF and HFS compared with the C group. The levels of oxidant and antioxidant proteins showed no difference between the groups. CONCLUSION: HF and HFS dietary interventions promoted cardiac oxidative stress, in the presence and absence of obesity, respectively. However, this process was neither mediated by the pro-oxidants AT1 and Nox2, nor by the quantitative reduction of antioxidant enzymes.

Moderate-intensity aerobic training reduces cardiac damage attributable to experimental iron overload in rats.

NEW FINDINGS: What is the central question of this study? The current literature indicates that oxidative stress plays a major role in iron overload. Although exercise is a well-established approach to treat/prevent cardiovascular diseases, its effects on iron overload are not known. What is the main finding and its importance? Moderate-intensity aerobic training had benefits in a rodent model of iron-overload cardiomyopathy by improving the antioxidant capacity of the heart. After further confirmation by translational and clinical studies, we should consider using this non-pharmacological, highly accessible and easily executable adjuvant approach allied to other therapies to improve the quality of life of iron-overloaded patients. ABSTRACT: Iron is an essential micronutrient for several life processes, but its excess can damage organs owing to oxidative stress, with cardiomyopathy being the leading cause of death in iron-overloaded patients. Although exercise has long been considered as a cardioprotective tool, its effects on iron overload are not known. This study was designed to investigate the effects of moderate-intensity aerobic training in rats previously submitted to chronic iron overload. Wistar rats received i.p. injections of iron dextran (100 mg/kg, 5 days/week for 4 weeks); thereafter, the rats were kept sedentary or exercised (60 min/day, progressive aerobic training, 60-70% of maximal speed, 5 days/week on a treadmill) for 8 weeks. At the end of the experimental period, haemodynamics were recorded and blood samples, livers and hearts harvested. Myocardial mechanics of papillary muscles were assessed in vitro, and cardiac remodelling was evaluated by histology and immunoblotting. Iron overload led to liver iron deposition, liver fibrosis and increased serum alanine aminotransferase and aspartate aminotransferase. Moreover, cardiac iron accumulation was accompanied by impaired myocardial mechanics, increased cardiac collagen type I and lipid peroxidation (TBARS), and release of creatine phosphokinase-MB to the serum. Although exercise did not influence iron levels, tissue injury markers were significantly reduced. Likewise, myocardial contractility and inotropic responsiveness were improved in exercised rats, in association with an increase in the endogenous antioxidant enzyme catalase. In conclusion, moderate-intensity aerobic exercise was associated with attenuated oxidative stress and cardiac damage in a rodent model of iron overload, thereby suggesting its potential role as a non-pharmacological adjuvant therapy for iron-overload cardiomyopathy.

Digoxin Combined with Aerobic Interval Training Improved Cardiomyocyte Contractility.

Digoxin is a cardiotonic that increases the cardiac output without causing deleterious effects on heart, as well as improves the left ventricular performance during physical exercise. We tested whether the association between chronic digoxin administration and aerobic interval training (AIT) promotes beneficial cardiovascular adaptations by improving the myocardial contractility and calcium (Ca2+) handling. Male Wistar rats were randomly assigned to sedentary control (C), interval training (T), sedentary digoxin (DIGO) and T associated to digoxin (TDIGO). AIT was performed on a treadmill (1h/day, 5 days/week) for 60 days, consisting of successive 8-min periods at 80% and 20% of VO2máx for 2 min. Digoxin was administered by orogastric gavage for 60 days. Left ventricle samples were collected to analysis of Ca2+ handling proteins; contractility and Ca2+ handling were performed on isolated cardiomyocytes. TDIGO group had a greater elevation in fractional shortening (44%) than DIGO, suggesting a cardiomyocyte contractile improvement. In addition, T or TDIGO groups showed no change in cardiomyocytes properties after Fura2-acetoxymethyl ester, as well as in sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban and calcineurin expressions. The main findings indicate that association of digoxin and aerobic interval training improved the cardiomyocyte contractile function, but these effects seem to be unrelated to Ca2+ handling.

Short-Term Cigarette Smoking in Rats Impairs Physical Capacity and Induces Cardiac Remodeling.

Despite the strong evidence on the cardiac and renal damages after chronic exposure to cigarette smoke, there is a paucity of data on its short-term effects. The study evaluated the short-term effects of cigarette smoking on left ventricular (LV) remodeling, in vitro myocardial and renal function. Female Wistar rats were randomized to control (C) and cigarette smoking rats for eight weeks. Physical capacity was assessed using an adapted model of exhaustive swim; left ventricle (LV) morphology and function were also evaluated. Renal function was assessed by creatinine clearance and urine protein. The in vitro myocardial performance was analyzed in isolated papillary muscles. Rats exhibited reduced physical capacity after short-term cigarette smoking. Although there was no change on LV function, reduced chamber diameter was found in the smoking group associated with an increased LV wall thickness. There was augmented cardiac mass compared to C that was confirmed by increased cardiomyocyte nucleus volume, but in vitro myocardial performance and renal function were unchanged. A short-term cigarette smoking induces cardiac remodeling without abnormalities in function. The smoking group still preserved renal function and in vitro myocardial performance. However, the reduced physical capacity may suggest an impairment of the cardiac reserve.

Effects of kettlebell training and detraining on mood status and sleep and life quality of healthy women.

BACKGROUND AND PURPOSE: Kettlebell exercise have become popular because of its ability to simultaneously train aerobic/anaerobic systems, low cost and easy access, and the great potential for physical fitness programs with a focus on public health. However, little is known about its effects on mood status, sleep, and quality of life (QOL) parameters. The aim of the present study was to examine the effects of kettlebell training/detraining on the prevention of depressive and anxiety symptoms and QOL and sleep quality. METHODS: The sample was composed of 17 healthy women (age: 26.0 ± 5.0 years; body mass: 60.9 ± 12.5 kg; height: 164.6 ± 5.5 cm). The study was organized into four consecutive phases: pre-intervention (PRE), intervention (kettlebell training, 12 weeks, three times/week), post-intervention (POST) and detraining (D, four weeks). The questionnaires SF-36 (QOL), Beck (depressive symptoms), State-Anxiety Inventory (acute anxiety symptoms), POMS (mood state) and the Pittsburgh Sleep Quality Index (sleep quality) were administered at PRE/POST/D phases. RESULTS: QOL, anxiety, sleep quality, and mood state exhibited no differences between PRE/POST/D. Levels of depressive symptoms significantly decreased (22.0%, p = 0.003) between PRE and POST phases, and remained low and similar to POST levels after D. CONCLUSION: Twelve weeks of kettlebell training was able to reduce and prevent depressive/anxiety symptoms in healthy women and these results were maintained after short-term detraining. Thus, kettlebell training might be considered an alternative method on the promotion of mental health and prevention of mood disorders and consequently can improve QOL even in health people.

Resistance training promotes reduction in Visceral Adiposity without improvements in Cardiomyocyte Contractility and Calcium handling in Obese Rats.

Resistance training (RT) improves the cardiomyocyte calcium (Ca2+) cycling during excitation-contraction coupling. However, the role of RT in cardiomyocyte contractile function associated with Ca2+ handling in obesity is unclear. Wistar rats were distributed into four groups: control, sedentary obese, control plus RT, and obesity plus RT. The 10-wk RT protocol was used (4-5 vertical ladder climbs, 60-second interval, 3× a week, 50-100% of maximum load). Metabolic, hormonal, cardiovascular and biochemical parameters were determined. Reduced leptin levels, epididymal, retroperitoneal and visceral fat pads, lower body fat, and adiposity index were observed in RT. Obesity promoted elevation of collagen, but RT did not promote modifications of LV collagen in ObRT. RT induced elevation in maximum rates of contraction and relaxation, and reduction of time to 50% relaxation. ObRT group did not present improvement in the cardiomyocyte contractile function in comparison to Ob group. Reduced cardiac PLB serine16 phosphorylation (pPLB Ser16) and pPLB Ser16/PLB ratio with no alterations in sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and phospholamban (PLB) expression were observed in Ob groups. Resistance training improved body composition reduced fat pads and plasma leptin levels but did not promote positive alterations in cardiomyocyte contractile function, Ca2+ handling and phospholamban phosphorylation.

Myocardial Dysfunction after Severe Food Restriction Is Linked to Changes in the Calcium-Handling Properties in Rats.

Severe food restriction (FR) impairs cardiac performance, although the causative mechanisms remain elusive. Since proteins associated with calcium handling may contribute to cardiac dysfunction, this study aimed to evaluate whether severe FR results in alterations in the expression and activity of Ca2+-handling proteins that contribute to impaired myocardial performance. Male 60-day-old Wistar-Kyoto rats were fed a control or restricted diet (50% reduction in the food consumed by the control group) for 90 days. Body weight, body fat pads, adiposity index, as well as the weights of the soleus muscle and lung, were obtained. Cardiac remodeling was assessed by morphological measures. The myocardial contractile performance was analyzed in isolated papillary muscles during the administration of extracellular Ca2+ and in the absence or presence of a sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) specific blocker. The expression of Ca2+-handling regulatory proteins was analyzed via Western Blot. Severe FR resulted in a 50% decrease in body weight and adiposity measures. Cardiac morphometry was substantially altered, as heart weights were nearly twofold lower in FR rats. Papillary muscles isolated from FR hearts displayed mechanical dysfunction, including decreased developed tension and reduced contractility and relaxation. The administration of a SERCA2a blocker led to further decrements in contractile function in FR hearts, suggesting impaired SERCA2a activity. Moreover, the FR rats presented a lower expression of L-type Ca2+ channels. Therefore, myocardial dysfunction induced by severe food restriction is associated with changes in the calcium-handling properties in rats.

High-Fat Diet-Induced Obesity Model Does Not Promote Endothelial Dysfunction via Increasing Leptin/Akt/eNOS Signaling.

Experimental studies show that the unsaturated high-fat diet-induced obesity promotes vascular alterations characterized by improving the endothelial L-arginine/Nitric Oxide (NO) pathway. Leptin seems to be involved in this process, promoting vasodilation via increasing NO bioavailability. The aim of this study was to test the hypothesis that unsaturated high-fat diet-induced obesity does not generate endothelial dysfunction via increasing the vascular leptin/Akt/eNOS signaling. Thirty-day-old male Wistar rats were randomized into two groups: control (C) and obese (Ob). Group C was fed a standard diet, while group Ob was fed an unsaturated high-fat diet for 27 weeks. Adiposity, hormonal and biochemical parameters, and systolic blood pressure were observed. Concentration response curves were performed for leptin or acetylcholine in the presence or absence of Akt and NOS inhibitor. Our results showed that an unsaturated high-fat diet promoted a greater feed efficiency (FE), elevation of body weight and body fat (BF), and an adiposity index, characterizing a model of obesity. However, comorbidities frequently associated with experimental obesity were not visualized, such as glucose intolerance, dyslipidemia and hypertension. The evaluation of the endothelium-dependent relaxation with acetylcholine showed no differences between the C and Ob rats. After NOS inhibition, the response was completely abolished in the Ob group, but not in the C group. Furthermore, Akt inhibition completely blunted vascular relaxation in the C group, but not in the Ob group, which was more sensitive to leptin-induced vascular relaxation. L-NAME incubation abolished the relaxation in both groups at the same level. Although Akt inhibitor pre-incubation reduced the leptin response, group C was more sensitive to its effect. In conclusion, the high-unsaturated fat diet-induced obesity improved the vascular reactivity to leptin and does not generate endothelial dysfunction, possibly by the increase in the vascular sensitivity to leptin and increasing NO bioavailability. Moreover, our results suggest that the increase in NO production occurs through the increase in NOS activation by leptin and is partially mediated by the Akt pathway.

Prevalence of overweight and obesity in elementary school students of Vitória, ES / Prevalência de sobrepeso e obesidade em escolares do ensino fundamental de Vitória/ES

Although numerous studies have analyzed overweight and obesity among schoolchildren from various Brazilian regions, the data relative to the state of Espírito Santo (ES) remains scarce. Considering the information presented, the purpose of present study was to investigate the prevalence of overweight and obesity among elementary school students from Vitória, ES. This was a cross-sectional study including 572 school children between 7 to 14 years old enrolled in municipal elementary schools in Vitória, ES, totalling 310 girls and 262 boys, who were randomly selected by stratified cluster sampling. The prevalence of overweight and obesity was calculated based on the children's anthropometric profile according to percentage of body fat by measuring skinfold thickness and body mass index (BMI). Based on BMI, the prevalence of overweight was high in both sexes, with 20.6% among the boys and 20.9% among the girls. The prevalence of obesity did not differ between boys and girls, with 6.5% and 7.7%, respectively. The results of the skin-fold thickness of skin show that 31.3% of children attending municipal schools in Vitória/ES were classified as overweight. In summary, the current study found a high prevalence of overweight and obesity, reaffirming that the overweight reaches a significant proportion of children and adolescents who attend public elementary schools in the city of Vitória, ES

Embora numerosos estudos tenham analisado o sobrepeso e a obesidade entre escolares de várias regiões brasileiras, dados relativos ao estado do Espírito Santo (ES) ainda são escassos. Considerando as informações destacadas acima, o objetivo do presente estudo foi investigar a prevalência de sobrepeso e obesidade em crianças do ensino fundamental de Vitória/ ES. Estudo transversal com 572 escolares de 7 a 14 anos matriculados em escolas municipais do ensino fundamental de Vitória/ES, totalizando 310 meninas e 262 meninos, selecionados aleatoriamente por amostra de estratificada por conglomerados. A prevalência de sobrepeso e obesidade foi calculada com base no perfil antropométrico das crianças de acordo com a porcentagem de gordura corporal, medindo-se a espessura das dobras cutâneas e o índice de massa corporal (IMC). Com base no IMC, a prevalência de excesso de peso foi alta em ambos os sexos, com 20,6% entre os meninos e 20,9% entre as meninas. Os resultados da espessura da prega cutânea demonstram que 31,3% das crianças que frequentavam escolas municipais em Vitória/ES foram classificadas com excesso de peso. Em conclusão, o presente estudo encontrou alta prevalência de sobrepeso e obesidade, reafirmando que o excesso de peso atinge uma proporção significativa das crianças e adolescentes que frequentam escolas municipais em Vitória / ES

Fasting/Refeeding Cycles Prevent Myocardial Dysfunction and Morphology Damage in the Spontaneously Hypertensive Rats / Ciclos de Jejum/Realimentação Previnem Disfunção Miocárdica e Danos Morfológicos em Ratos Espontaneamente Hipertensos

Abstract Background: Caloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown. Objective: To investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca2+ handling and b-adrenergic system. Methods: Sixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R50) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% (a = 0.05). Results: The RF rats presented lower cardiac atrophy than R50 in relation to C rats. The C rats increased weight gain, R50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R50 rats. In addition, the R50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils. Conclusion: Fasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca2+ handling and b-adrenergic system.

Resumo Fundamento: A restrição calórica compromete a função e a morfologia cardíacas em corações hipertrofiados de ratos espontaneamente hipertensos (SHR). No entanto, a influência de ciclo de jejum/Realimentação é desconhecida. Objetivo: Investigar o efeito de ciclos de jejum/realimentação sobre a remodelação e função miocárdica. Além disso, o presente estudo foi desenhado para avaliar os mecanismos subjacentes à participação do trânsito de cálcio (Ca+2) e sistema beta-adrenérgico. Métodos: Neste estudo, SHR machos de 60 dias de idade foram submetidos a alimento ad libitum (grupo C), 50% de restrição alimentar (grupo R50) ou ciclos de RF (grupo RF) por 90 dias. A remodelação cardíaca foi avaliada por meio da análise ultraestrutural e função do músculo papilar isolado. Adotou-se o nível de significância de 5% (a = 0,05). Resultados: Os ratos do grupo RF apresentaram menor atrofia cardíaca do que os do grupo R50 em relação aos do grupo C. Os ratos do grupo C aumentaram peso corporal, os ratos do grupo R50 mantiveram seu peso corporal inicial e os ratos do grupo RF aumentaram e reduziram seu peso durante o ciclo RF. O ciclo RF não causou comprometimento funcional, pois os parâmetros isotônicos e isométricos apresentaram comportamento similar aos dos ratos do grupo C. Os parâmetros cardíacos isotônicos e isométricos mostraram-se significativamente elevados nos ratos do grupo RF em comparação aos dos ratos do grupo R50. Além disso, os ratos do grupo R50 apresentaram dano cardíaco em comparação aos ratos do grupo C quanto às variáveis isotônicas e isométricas. Os ratos do grupo R50 apresentaram alterações focais em muitas fibras musculares, enquanto os ratos do grupo RF apresentaram leves alterações, como perda ou desorganização de miofibrilas. Conclusão: Ciclos de Jejum/Realimentação promovem efeitos benéficos cardíacos e atenuam o dano miocárdico causado por restrição calórica em SHR, contribuindo para reduzir o risco cardiovascular e os danos morfológicos. Além disso, o ciclo de jejum/realimentação promove leve melhora do trânsito do Ca2+ e do sistema beta-adrenérgico.

Fasting/Refeeding Cycles Prevent Myocardial Dysfunction and Morphology Damage in the Spontaneously Hypertensive Rats.

BACKGROUND: Caloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown. OBJECTIVE: To investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca2+ handling and b-adrenergic system. METHODS: Sixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R50) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% (a = 0.05). RESULTS: The RF rats presented lower cardiac atrophy than R50 in relation to C rats. The C rats increased weight gain, R50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R50 rats. In addition, the R50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils. CONCLUSION: Fasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca2+ handling and b-adrenergic system.