Cardiac, Metabolic and Molecular Profiles of Sedentary Rats in the Initial Moment of Obesity / Perfis Cardíaco, Metabólico e Molecular de Ratos Sedentários no Momento Inicial da Obesidade

Abstract Background: Different types of high-fat and/or high-energy diets have been used to induce obesity in rodents. However, few studies have reported on the effects observed at the initial stage of obesity induced by high-fat feeding on cardiac functional and structural remodelling. Objective: To characterize the initial moment of obesity and investigate both metabolic and cardiac parameters. In addition, the role of Ca2+ handling in short-term exposure to obesity was verified. Methods: Thirty-day-old male Wistar rats were randomized into two groups (n = 19 each): control (C; standard diet) and high-fat diet (HF, unsaturated high-fat diet). The initial moment of obesity was defined by weekly measurement of body weight (BW) complemented by adiposity index (AI). Cardiac remodelling was assessed by morphological, histological, echocardiographic and papillary muscle analysis. Ca2+ handling proteins were determined by Western Blot. Results: The initial moment of obesity occurred at the 3rd week. Compared with C rats, the HF rats had higher final BW (4%), body fat (20%), AI (14.5%), insulin levels (39.7%), leptin (62.4%) and low-density lipoprotein cholesterol (15.5%) but did not exhibit alterations in systolic blood pressure. Echocardiographic evaluation did not show alterations in cardiac parameters. In the HF group, muscles were observed to increase their +dT/dt (C: 52.6 ± 9.0 g/mm2/s and HF: 68.0 ± 17.0 g/mm2/s; p < 0.05). In addition, there was no changes in the cardiac expression of Ca2+ handling proteins. Conclusion: The initial moment of obesity promotes alterations to hormonal and lipid profiles without cardiac damage or changes in Ca2+ handling.

Resumo Fundamentos: Diferentes tipos de dietas hiperlipídicas e/ou hipercalóricas têm sido usados para induzir obesidade em roedores. No entanto, poucos estudos relataram os efeitos da obesidade induzida por dieta hiperlipídica em sua fase inicial sobre a remodelação cardíaca funcional e estrutural. Objetivo: Caracterizar o momento inicial da obesidade e investigar parâmetros metabólicos e cardíacos. Além disso, analisar o papel do trânsito de Ca+2 em curtos períodos de exposição à obesidade. Métodos: Ratos Wistar com idade de 30 dias foram distribuídos aleatoriamente em dois grupos (n = 19 em cada grupo): controle (C, dieta padrão) e dieta hiperlipídica (HL, dieta rica em gordura insaturada). O momento inicial da obesidade foi definido por medidas semanais do peso corporal, complementadas pelo índice de adiposidade (IA). A remodelação cardíaca foi avaliada por análise morfológica, histológica, ecocardiográfica e funcional dos músculos papilares. Proteínas envolvidas no trânsito de Ca2+ foram determinadas por Western Blot. Resultados: O momento inicial da obesidade ocorreu na terceira semana. Em comparação aos ratos C, os animais HL apresentaram maior peso corporal final (4%), gordura corporal (20%), IA (14,5%), níveis de insulina (39,7%), leptina (62,4%) e lipoproteína de baixa densidade (15,5%), mas não apresentaram alterações na pressão sistólica. A avaliação ecocardiográfica não mostrou alterações nos parâmetros cardíacos. No grupo HL, observou-se um aumento no +dT/dt (C: 52,6 ± 9,0 g/mm2/s e HL: 68,0 ± 17,0 g/mm2/s; p < 0,05) muscular. Além disso, não houve alterações na expressão cardíaca de proteínas envolvidas no trânsito de Ca2+. Conclusão: O momento inicial da obesidade promove alterações nos perfis hormonais e lipídicos sem causar danos cardíacos ou mudanças no trânsito de Ca2+.

Cardiac, Metabolic and Molecular Profiles of Sedentary Rats in the Initial Moment of Obesity.

BACKGROUND: Different types of high-fat and/or high-energy diets have been used to induce obesity in rodents. However, few studies have reported on the effects observed at the initial stage of obesity induced by high-fat feeding on cardiac functional and structural remodelling. OBJECTIVE: To characterize the initial moment of obesity and investigate both metabolic and cardiac parameters. In addition, the role of Ca2+ handling in short-term exposure to obesity was verified. METHODS: Thirty-day-old male Wistar rats were randomized into two groups (n = 19 each): control (C; standard diet) and high-fat diet (HF, unsaturated high-fat diet). The initial moment of obesity was defined by weekly measurement of body weight (BW) complemented by adiposity index (AI). Cardiac remodelling was assessed by morphological, histological, echocardiographic and papillary muscle analysis. Ca2+ handling proteins were determined by Western Blot. RESULTS: The initial moment of obesity occurred at the 3rd week. Compared with C rats, the HF rats had higher final BW (4%), body fat (20%), AI (14.5%), insulin levels (39.7%), leptin (62.4%) and low-density lipoprotein cholesterol (15.5%) but did not exhibit alterations in systolic blood pressure. Echocardiographic evaluation did not show alterations in cardiac parameters. In the HF group, muscles were observed to increase their +dT/dt (C: 52.6 ± 9.0 g/mm2/s and HF: 68.0 ± 17.0 g/mm2/s; p < 0.05). In addition, there was no changes in the cardiac expression of Ca2+ handling proteins. CONCLUSION: The initial moment of obesity promotes alterations to hormonal and lipid profiles without cardiac damage or changes in Ca2+ handling.

Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca2+ Handling / Resistência à Obesidade Promove Disfunção Contrátil Leve Associada com Trânsito Ca2+ Intracelular

Abstract Background: Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. Objective: To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. Methods: Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. Results: The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. Conclusion: Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling.

Resumo Fundamento: A obesidade induzida por dieta é frequentemente utilizada para demonstração de disfunção cardíaca. No entanto, alguns ratos, como humanos, são suscetíveis ao desenvolvimento de um fenótipo de obesidade, enquanto outros são resistentes. Objetivo: Avaliar a relação entre resistência à obesidade e função cardíaca e o impacto da resistência à obesidade no trânsito de cálcio. Métodos: Ratos Wistar machos com trinta dias de idade foram distribuídos em dois grupos com 54 animais cada: controle (C; dieta padrão) e obesos (quatro dietas palatáveis hiperlipídicas) por 15 semanas. Após o protocolo experimental, os ratos alimentados por dietas hiperlipídicas foram classificados de acordo com o índice de adiposidade e subdivididos em propensos à obesidade (PO) e resistentes à obesidade (RO). Foram avaliados o perfil nutricional, comorbidades e remodelação cardíaca. A função cardíaca foi avaliada pelo estudo do músculo papilar isolado em condições basais e após manobras inotrópicas. Resultados: As dietas hiperlipídicas promoveram aumento na gordura corporal e no índice de adiposidade em ratos PO comparados com ratos C e RO. Os perfis de glicose, lipídios e pressão arterial permaneceram inalterados em ratos RO. Além disso, os ratos RO apresentaram peso total do coração e dos ventrículos direito e esquerdo mais baixos do que ratos PO, mas semelhantes aos ratos C. Os músculos cardíacos de todos os ratos apresentaram dados semelhantes na condição basal, mas a resposta miocárdica a um estímulo de contração pós-pausa estava comprometida em ratos PO e RO em comparação aos ratos C. Conclusão: A resistência à obesidade promoveu alterações específicas na fase de contração, sem alterar a fase de relaxamento. Esta anormalidade leve pode estar relacionada com o trânsito intracelular de Ca+2.

Cardiac Dysfunction Induced by Obesity Is Not Related to ß-Adrenergic System Impairment at the Receptor-Signalling Pathway.

Obesity has been shown to impair myocardial performance. Some factors have been suggested as responsible for possible cardiac abnormalities in models of obesity, among them beta-adrenergic (ßA) system, an important mechanism of regulation of myocardial contraction and relaxation. The objective of present study was to evaluate the involvement of ßA system components in myocardial dysfunction induced by obesity. Thirty-day-old male Wistar rats were distributed in control (C, n = 25) and obese (Ob, n = 25) groups. The C group was fed a standard diet and Ob group was fed four unsaturated high-fat diets for 15 weeks. Cardiac function was evaluated by isolated papillary muscle preparation and ßA system evaluated by using cumulative concentrations of isoproterenol and Western blot. After 15 weeks, the Ob rats developed higher adiposity index than C rats and several comorbidities; however, were not associated with changes in systolic blood pressure. Obesity caused structural changes and the myocardial responsiveness to post-rest contraction stimulus and increased extracellular calcium (Ca2+) was compromised. There were no changes in cardiac function between groups after ßA stimulation. The obesity was not accompanied by changes in protein expression of G protein subunit alpha (Gsα) and ßA receptors (ß1AR and ß2AR). In conclusion, the myocardial dysfunction caused by unsaturated high-fat diet-induced obesity, after 15 weeks, is not related to ßAR system impairment at the receptor-signalling pathway.

Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca2+ Handling.

BACKGROUND: Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. OBJECTIVE: To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. METHODS: Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. RESULTS: The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. CONCLUSION: Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling.