Influência da intervenção com γ-orizanol na prevenção da síndrome metabólica cardiorrenal em ratos obesos
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2022-05-27
Autores
Garcia, Jéssica Leite [UNESP]
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Universidade Estadual Paulista (Unesp)
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Introdução: O padrão alimentar atual, conhecido como Dieta Ocidental, é caracterizado por alimentos de alta densidade energética ricos em açúcares e gordura, associado à prevalência da obesidade, um problema de saúde pública e plano de fundo para desenvolvimento de outras doenças como a síndrome metabólica cardiorrenal (SMCR). A SMCR define a coexistência de disfunção cardíaca e renal que compartilham mecanismos fisiopatológicos decorrentes da obesidade. Considerando a busca de alternativas para prevenir esses desfechos nocivos, o composto bioativo gama-orizanol (γOz) se destaca por apresentar efeitos benéficos, como a ação anti-inflamatória e antioxidante. Objetivo: Avaliar o efeito preventivo do γOz sobre a SMCR em modelo experimental de obesidade induzida por dieta rica em açúcares e gordura. Materiais e métodos: O estudo foi aprovado pela Comissão Ética no Uso de Animais da Faculdade de Medicina de Botucatu (1309/2019). 21 ratos Wistar, foram aleatoriamente distribuídos em 3 grupos: controle (n=7), high-sugar fat (HSF, n=7) e HSF + γOz (n=7), por 30 semanas. O grupo controle recebeu dieta padrão + água, os grupos HSF receberam dieta rica em açúcares e gordura + água acrescida da 25% de sacarose. O grupo HSF + γOz recebeu o composto isolado na dose de 0.5% adicionado à ração. O peso corporal foi acompanhamento semanalmente. Na 30ª semana, foram realizadas as análises de pressão arterial sistólica, ecocardiograma e coleta de urina 24 horas. Posteriormente, os animais foram submetidos a jejum por 8 horas e à eutanásia. Foram coletados o plasma, para analises metabólicas, depósitos de gordura corporal para caracterizar a obesidade, coração e rins para análise do proteoma. Dados paramétricos estão apresentados em média e desvio padrão e não-paramétricos apresentados em mediana e intervalo interquartil, analisados por ANOVA uma via seguido de teste post-hoc de Tukey ou Kruskall Wallis seguindo de teste de Dunn’s, respectivamente. Valores de p<0,05 foram considerados significantes. Resultados: O grupo HSF apresentou maior peso corporal e índice de adiposidade, níveis plasmáticos elevados de glicose, triglicérides, insulina e aumento da AUC (tolerância a glicose) e índice de resistência à insulina. A disfunção renal foi marcada por aumento da razão proteína/creatinina e diminuição da taxa de filtração glomerular e, no coração, foi verificada a presença de alterações estruturais e disfunção sistólica. O γOz preveniu a obesidade, elevação dos níveis de triglicérides, intolerância à glicose e resistência à insulina, assim como a disfunção em ambos os órgãos estudados. No tecido renal, o composto atuou sobre os processos biológicos de formação de espécies reativas de oxigênio, estresse oxidativo e proteínas da cadeia respiratória mitocondrial. No tecido cardíaco, o γOz atuou sobre os processos de síntese lipídica, fibrose, proteínas envolvidas na contratilidade cardíaca e também da cadeia respiratória mitocondrial. Conclusão: O O γOz preveniu alterações no proteoma renal e cardíaco relacionadas ao estresse oxidativo e função mitocondrial, mecanismos fundamentais para o desenvolvimento da doença.
Introduction: The Western Diet is characterized by high energy density foods rich in sugars and fat which is associated with the prevalence of obesity, a public health problem and the onset for the development of other diseases such as cardiorenal metabolic syndrome (CRMS). The SMCR defines the coexistence of cardiac and renal dysfunction sharing pathophysiological mechanisms. Considering the search for alternatives to prevent these harmful outcomes, the bioactive compound gamma-oryzanol (γOz) is highlighted for its beneficial effects, such as anti-inflammatory and antioxidant action. Aim: To evaluate the preventive effect of γOz on the CRMS in a high sugar-fat-induced obesity model. Materials and methods: The study was approved by the Ethics Committee on the Use of Animals (1309/2019). 21 Wistar rats were randomly distributed into 3 groups: control (n=7), high-sugar fat (HSF, n=7) and HSF + γOz (n=7), for 30 weeks. The control group received a standard diet + water, the HSF groups received the high sugar-fat diet + 25% sucrose in drinking water. The HSF + γOz group received the isolated compound at the dose of 0.5% added to the diet. Body weight was monitored weekly. At the 30th week, systolic blood pressure, echocardiogram and 24-hour urine collection were performed. Subsequently, the animals were fasted for 8 hours and euthanized. Plasma were collected for metabolic analysis, body fat deposits to characterize obesity, heart and kidneys for proteome analysis. Parametric data are presented as mean and standard deviation and non-parametric data are presented as median and interquartile range, analyzed by one-way ANOVA followed by Tukey's post-hoc or Kruskall Wallis test followed by Dunn's test, respectively. Values of p<0.05 were considered significant. Results: The HSF group presented higher body weight and adiposity index, higher plasma levels of glucose, triglycerides, insulin and increased AUC (glucose tolerance) and insulin resistance index. Renal dysfunction was marked by an increase in the protein/creatinine ratio and a decrease in the glomerular filtration rate and, in the heart, it was observed structural alterations and systolic dysfunction. γOz prevented obesity, elevation of triglycerides levels, glucose intolerance and insulin resistance, as well as the dysfunction of both organs studied. In kidney tissue, the compound acted on the biological processes of formation of reactive oxygen species, oxidative stress and mitochondrial respiratory chain proteins. In cardiac tissue, γOz acted on the processes of lipid synthesis, fibrosis, proteins involved in cardiac contractility and also on the mitochondrial respiratory chain. Conclusion: The γOz prevented changes in the kidney and heart proteome related to oxidative stress and mitochondrial function, key mechanisms for the development of the disease.
Introduction: The Western Diet is characterized by high energy density foods rich in sugars and fat which is associated with the prevalence of obesity, a public health problem and the onset for the development of other diseases such as cardiorenal metabolic syndrome (CRMS). The SMCR defines the coexistence of cardiac and renal dysfunction sharing pathophysiological mechanisms. Considering the search for alternatives to prevent these harmful outcomes, the bioactive compound gamma-oryzanol (γOz) is highlighted for its beneficial effects, such as anti-inflammatory and antioxidant action. Aim: To evaluate the preventive effect of γOz on the CRMS in a high sugar-fat-induced obesity model. Materials and methods: The study was approved by the Ethics Committee on the Use of Animals (1309/2019). 21 Wistar rats were randomly distributed into 3 groups: control (n=7), high-sugar fat (HSF, n=7) and HSF + γOz (n=7), for 30 weeks. The control group received a standard diet + water, the HSF groups received the high sugar-fat diet + 25% sucrose in drinking water. The HSF + γOz group received the isolated compound at the dose of 0.5% added to the diet. Body weight was monitored weekly. At the 30th week, systolic blood pressure, echocardiogram and 24-hour urine collection were performed. Subsequently, the animals were fasted for 8 hours and euthanized. Plasma were collected for metabolic analysis, body fat deposits to characterize obesity, heart and kidneys for proteome analysis. Parametric data are presented as mean and standard deviation and non-parametric data are presented as median and interquartile range, analyzed by one-way ANOVA followed by Tukey's post-hoc or Kruskall Wallis test followed by Dunn's test, respectively. Values of p<0.05 were considered significant. Results: The HSF group presented higher body weight and adiposity index, higher plasma levels of glucose, triglycerides, insulin and increased AUC (glucose tolerance) and insulin resistance index. Renal dysfunction was marked by an increase in the protein/creatinine ratio and a decrease in the glomerular filtration rate and, in the heart, it was observed structural alterations and systolic dysfunction. γOz prevented obesity, elevation of triglycerides levels, glucose intolerance and insulin resistance, as well as the dysfunction of both organs studied. In kidney tissue, the compound acted on the biological processes of formation of reactive oxygen species, oxidative stress and mitochondrial respiratory chain proteins. In cardiac tissue, γOz acted on the processes of lipid synthesis, fibrosis, proteins involved in cardiac contractility and also on the mitochondrial respiratory chain. Conclusion: The γOz prevented changes in the kidney and heart proteome related to oxidative stress and mitochondrial function, key mechanisms for the development of the disease.
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Palavras-chave
Dieta ocidental, Obesidade, Disfunção cardíaca, Disfunção renal, Gama-orizanol, Proteômica, Síndrome metabólica