title: Oral formulation of angiotensin-(1-7) improves lipid metabolism and prevents high-fat diet-induced hepatic steatosis and inflammation in mice.
abstract: 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.
authors.affiliation: Department of Pharmacology, Universidade Federal de Minas Gerais, Av Antonio Carlos 6627-ICB, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: John David
authors.initials: JD
authors.lastname: Feltenberger
authors.forename: João Marcus Oliveira
authors.initials: JM
authors.lastname: Andrade
authors.forename: Alanna
authors.initials: A
authors.lastname: Paraíso
authors.forename: Lucas Oliveira
authors.initials: LO
authors.lastname: Barros
authors.forename: Aristides Batista Maia
authors.initials: AB
authors.lastname: Filho
authors.forename: Ruben D M
authors.initials: RD
authors.lastname: Sinisterra
authors.forename: Frederico B
authors.initials: FB
authors.lastname: Sousa
authors.forename: André Luiz Sena
authors.initials: AL
authors.lastname: Guimarães
authors.forename: Alfredo Mauricio Batista
authors.initials: AM
authors.lastname: de Paula
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Campagnole-Santos
authors.forename: Mahboob
authors.initials: M
authors.lastname: Qureshi
authors.forename: Robson Augusto Souza
authors.initials: RA
authors.lastname: dos Santos
authors.forename: Sérgio Henrique Sousa
authors.initials: SH
authors.lastname: Santos
mesh_terms: D000284:Administration, Oral; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000517:prevention & control*; D007249:Inflammation / Q000517:prevention & control*; D015850:Interleukin-6 / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D015850:Interleukin-6; D010446:Peptide Fragments; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014409:Tumor Necrosis Factor-alpha; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: angiotensina-(1–7); fatty liver; lipid metabolism; obesity; visceral steatosis, congenital