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 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.
- Received December 21, 2012.
- Revision received January 14, 2013.
- Accepted May 15, 2013.
- © 2013 American Heart Association, Inc.