Papel da suplementação com licopeno sobre o remodelamento cardíaco induzido por dieta: modelo experimental de obesidade em ratos
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Data
2019-12-17
Autores
Silva, Carol Cristina Vagula de Almeida
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Universidade Estadual Paulista (Unesp)
Resumo
A obesidade é uma doença metabóliconutricional comum em países industrializados, com impacto financeiro na saúde pública. A interface entre hiperadiposidade e inflamação é bem conhecida. Evidências mostram que mediadores inflamatórios e metaloproteinase-2 estão relacionados ao remodelamento cardíaco. Várias estratégias terapêuticas têm sido testadas, como o uso de compostos bioativos. Nenhum estudo abordou o efeito do licopeno sobre o remodelamento cardíaco induzido associado a obesidade. Objetivo: O objetivo geral do presente estudo foi verificar o efeito da suplementação com licopeno sobre o remodelamento cardíaco em ratos com obesidade induzida por dieta hipercalórica com alto teor de carboidrato. Metodologia: Ratos Wistar machos, 200g (n=40), foram randomizados em dois grupos com diferentes tratamentos dietéticos ad libitum: dieta padrão (C, n=20) ou dieta obesogênica (CHO, n=20) por 20 semanas.O grupo C recebeu dieta padrão + água. Com o objetivo de induzir obesida-de1, o grupo CHO recebeu dieta com alto teor de carboidrato simples e gordura + água acrescida de sacarose 25% (total de carboidratos: 78%, total de gordura: 16,54%). Após a 20ª semana, foi iniciada a suplementação com licopeno (10mg/kg de peso/dia) ou veículo (óleo de milho) por 10 semanas via gavage. Assim, após a 20ª semana, os grupos foram subdivididos da seguinte maneira: grupo Controle (C, n=10); Controle+licopeno (C + Ly, n=10); Carboidrato (CHO, n=10) e Carboidrato+licopeno (CHO + Ly, n=10). Na 20ª e 30ª semana, os animais foram submetidos à aferição da pressão arterial sistólica (PAS) e avaliação ecocardiográfica morfológica e funcional. Ao final do experimento (30ª semana), os animais foram eutanasiados sob profunda anestesia (tiopental 120 mg/kg de m.c. via IP) e decaptados para obtenção de amostras de sangue e de coração. Foram estudados também: índice de adiposidade; ingestão calórica, ingestão total de ração, ingestão de líquidos, ganho de peso, eficiência alimentar, resistência à insulina, marcadores bioquímicos, citocinas inflamatórias no coração e no tecido adiposo, atividade de metaloproteinase-2, biodisponibilidade do licopeno no coração, avaliação ecocardiográfica. Resultados: Na 20ª semana foram detectadas alterações características de remodelamento cardíaco patológico, resistência à insulina, e hipertensão nos animais do grupo CHO. Na 30ª semana foi detectado aumento do índice de adiposidade e as alterações já detectadas na 20ª (remodelamen-to cardíaco patológico, a resistência à insulina e hipertensão) nos animais do grupo CHO (vs. C). Além disso foi verificado que o grupo CHO (vs. C) apresentou aumento da inflamação no coração e no tecido adiposo, maior ativação de metaloproteinase-2 no coração. A suplementação com licopeno nos animais do grupo CHO+Ly (vs. CHO) foi capaz de melhorar a resistência à insulina e resistência à insulina, além de atenuar remodelamento, inflamação, ativação de metaloproteinase-2 no coração. Conclusão: A dieta foi capaz de promover obesidade, remodelamento cardíaco patológico, resistência à insulina, hipertensão, inflamação cardíaca e no tecido adiposo, e maior ativação de metaloproteinase-2 no coração. A suplementação com licopeno foi capaz de melhorar alterações associadas a obesidade, como insulina, resistência à insulina, e remodelamento, inflamação, ativação de metaloproteinase-2 no coração. Esses dados sugerem que o licopeno pode corresponder a uma nova estratégia terapêutica coadjuvante no tratamento das alterações associadas a obesidade.
Obesity is a metabolic-nutritional disease common in industrialized countries, with financial impact on public health. The interface between hyperadiposity and inflammation is well known. Evidence shows that inflammatory mediators and metalloproteinase-2 are related to cardiac remodeling. Several therapeutic strategies have been tested, such as the use of bioactive compounds. No study has addressed the effect of lycopene on obesity-induced cardiac remodeling. Objective: The general objective of the present study was to verify the effect of lycopene supplementation on cardiac remodeling in rats with obesity induced by high carbohydrate diet. Methodology: Male Wistar rats, 200g (n=40), were randomized into two groups with different ad libitum dietary treatments: standard diet (C, n=20) or obesogenic diet (CHO, n=20) for 20 weeks. C received standard diet+water. Aiming to induce obesity, the CHO group received a diet with high simple carbohydrate and fat + water plus 25% sucrose (total carbohydrate: 78%, total fat: 16.54%). After the 20th week, supplementation with lycopene (10mg / kg weight / day) or vehicle (corn oil) were administered by gavage for 10 weeks. Thus, after the 20th week, the groups were subdivided as follows: Control group (C, n = 10); Control + lycopene (C+Ly, n = 10); Carbohydrate (CHO, n = 10) and Carbohydrate + lycopene (CHO+Ly, n=10). At week 20 and 30, the animals underwent systolic blood pressure (SBP), morphological and functional echocardiographic evaluation. At the end of the experiment (week 30), the animals were euthanized under deep anesthesia (thiopental 120 mg / kg m.c. via IP) and decapitated to obtain blood and heart samples. Adiposity index, caloric intake, weight gain, feed efficiency, insulin resistance, biochemical markers, inflammatory cytokines in the heart, metalloproteinase-2 activity, lycopene bioavailability in the heart, echocardiographic evaluation were also determined. Results: At 20th week, pathological cardiac remodeling, insulin resistance, and hypertension were detected in the animals of the CHO group (vs. C). At 30th week was identified the changes described above, besides an increase in adiposity index (CHO vs. C). In addition, animals from CHO group (vs. C) exhibited an increased inflammation in the heart and adipose tissues, and an augmented cardiac metalloproteinase-2 activation. Lycopene supplementation in animals from CHO + Ly group (vs. CHO) was able to improve, insulin, insulin resistance, as well as attenuating remodeling, inflammation, and activation of metalloproteinase-2 in the heart. Conclusion: The diet was able to promote obesity, pathological cardiac remodeling, insulin resistance, hypertension, cardiac and adipose tissue inflammation, and increased the activation of metalloproteinase-2 in the heart. Lycopene supplementation was able to improve obesity-associated changes, such as insulin, insulin resistance, and remodeling, inflammation, and activation of metalloproteinase-2 in the heart. These data suggest that lycopene may correspond to a new ancillary therapeutic strategy in the treatment of obesity-associated changes.
Obesity is a metabolic-nutritional disease common in industrialized countries, with financial impact on public health. The interface between hyperadiposity and inflammation is well known. Evidence shows that inflammatory mediators and metalloproteinase-2 are related to cardiac remodeling. Several therapeutic strategies have been tested, such as the use of bioactive compounds. No study has addressed the effect of lycopene on obesity-induced cardiac remodeling. Objective: The general objective of the present study was to verify the effect of lycopene supplementation on cardiac remodeling in rats with obesity induced by high carbohydrate diet. Methodology: Male Wistar rats, 200g (n=40), were randomized into two groups with different ad libitum dietary treatments: standard diet (C, n=20) or obesogenic diet (CHO, n=20) for 20 weeks. C received standard diet+water. Aiming to induce obesity, the CHO group received a diet with high simple carbohydrate and fat + water plus 25% sucrose (total carbohydrate: 78%, total fat: 16.54%). After the 20th week, supplementation with lycopene (10mg / kg weight / day) or vehicle (corn oil) were administered by gavage for 10 weeks. Thus, after the 20th week, the groups were subdivided as follows: Control group (C, n = 10); Control + lycopene (C+Ly, n = 10); Carbohydrate (CHO, n = 10) and Carbohydrate + lycopene (CHO+Ly, n=10). At week 20 and 30, the animals underwent systolic blood pressure (SBP), morphological and functional echocardiographic evaluation. At the end of the experiment (week 30), the animals were euthanized under deep anesthesia (thiopental 120 mg / kg m.c. via IP) and decapitated to obtain blood and heart samples. Adiposity index, caloric intake, weight gain, feed efficiency, insulin resistance, biochemical markers, inflammatory cytokines in the heart, metalloproteinase-2 activity, lycopene bioavailability in the heart, echocardiographic evaluation were also determined. Results: At 20th week, pathological cardiac remodeling, insulin resistance, and hypertension were detected in the animals of the CHO group (vs. C). At 30th week was identified the changes described above, besides an increase in adiposity index (CHO vs. C). In addition, animals from CHO group (vs. C) exhibited an increased inflammation in the heart and adipose tissues, and an augmented cardiac metalloproteinase-2 activation. Lycopene supplementation in animals from CHO + Ly group (vs. CHO) was able to improve, insulin, insulin resistance, as well as attenuating remodeling, inflammation, and activation of metalloproteinase-2 in the heart. Conclusion: The diet was able to promote obesity, pathological cardiac remodeling, insulin resistance, hypertension, cardiac and adipose tissue inflammation, and increased the activation of metalloproteinase-2 in the heart. Lycopene supplementation was able to improve obesity-associated changes, such as insulin, insulin resistance, and remodeling, inflammation, and activation of metalloproteinase-2 in the heart. These data suggest that lycopene may correspond to a new ancillary therapeutic strategy in the treatment of obesity-associated changes.
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Palavras-chave
Obesidade, Licopeno, Metaloproteinase 2 da matriz., Inflamação, Remodelação ventricular