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

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 hydroxypropyl-cyclodextrin (HPCD/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+HPCD, standard diet+Ang-(1-7)/HPCD, high-fat diet+HPCD, or high-fat diet+Ang-[1-7]/HPCD. 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- and interleukin-6. Expression of angiotensin converting enzyme, angiotensin-converting enzyme-2, interleukin-1, tumor necrosis factor-, interleukin-6, transforming growth factor-, acetyl-CoA carboxylase, carbohydrate-responsive element-binding protein, peroxisome proliferator-activated receptor-, 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- 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-, 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.