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Oral Formulation of Angiotensin-(1–7) Improves Lipid Metabolism and Prevents High-Fat Diet–Induced Hepatic Steatosis and Inflammation in Mice

2013; Lippincott Williams & Wilkins; Volume: 62; Issue: 2 Linguagem: Inglês

10.1161/hypertensionaha.111.00919

1524-4563

John David Feltenberger, João Marcus Oliveira Andrade, Alanna Fernandes Paraíso, Lucas Oliveira Barros, Aristides Batista Maia Filho, Rubén D. Sinisterra, Frederico B. De Sousa, André Luiz Sena Guimarães, Alfredo Maurício Batista de Paula, Maria José Campagnole‐Santos, Mahboob Qureshi, Robson A.S. Santos, Sérgio Henrique Sousa Santos,

Apelin-related biomedical research

Angiotensin (Ang)-(1-7) has been described as an important tool on treating and preventing metabolic disorders. In this study, we aimed to evaluate the effect of an oral formulation of Ang-(1-7) included in hydroxypropylβ-cyclodextrin (HPβCD/Ang-[1-7]) on hepatic function, steatosis, and on liver inflammatory markers expression in mice treated with a high-fat diet. Male FVB/N mice were divided into 4 groups and fed for 60 days, with each group receiving 1 of the following diets: standard diet+HPβCD, standard diet+Ang-(1-7)/HPβCD, high-fat diet+HPβCD, or high-fat diet+Ang-[1-7]/HPβCD. Body weight, food intake, and blood parameters, such as total cholesterol, triglyceride, alaninetransaminases, and aspartate transaminases, were evaluated. Immunohistochemical analyses were performed for inflammatory markers tumor necrosis factor-α and interleukin-6. Expression of angiotensin converting enzyme, angiotensin-converting enzyme-2, interleukin-1β, tumor necrosis factor-α, interleukin-6, transforming growth factor-β, acetyl-CoA carboxylase, carbohydrate-responsive element-binding protein, peroxisome proliferator-activated receptor-γ, and sterol regulatory element-binding proteins-1c was evaluated by quantitative real-time polymerase chain reaction. The major findings of our study included reduced liver fat mass and weight, decreased plasma total cholesterol, triglyceride, and alaninetransaminase enzyme levels in the oral Ang-(1-7)-treated groups compared with the control groups. These results were accompanied by a significant reduction in tumor necrosis factor-α and interleukin-6 mRNA expression in the liver. Analyses of liver adipogenesis-related genes by quantitative real-time polymerase chain reaction showed that acetyl-CoA carboxylase, peroxisome proliferator-activated receptor-γ, and sterol regulatory element-binding proteins-1c mRNA expression were significantly suppressed. In conclusion, we observed that treatment with Ang-(1-7) improved metabolism and decreased proinflammatory profile and fat deposition in liver of mice.