Antioxidant Effects of Oral Ang-(1-7) Restore Insulin Pathway and RAS Components Ameliorating Cardiometabolic Disturbances in Rats

• Main Authors: Vivian Paulino Figueiredo, Maria Andrea Barbosa, Uberdan Guilherme Mendes de Castro, Aline Cruz Zacarias, Frank Silva Bezerra, Renata Guerra de Sá, Wanderson Geraldo de Lima, Robson Augusto Souza dos Santos, Andréia Carvalho Alzamora
• Format: Article
• Language: English
• Published: Hindawi Limited 2019-01-01
• Series: Oxidative Medicine and Cellular Longevity
• Online Access: http://dx.doi.org/10.1155/2019/5868935
• ISSN: 1942-0900; 1942-0994

In prevention studies of metabolic syndrome (MetS), Ang-(1-7) has shown to improve the insulin signaling. We evaluated the HPβCD/Ang-(1-7) treatment on lipid metabolism, renin-angiotensin system (RAS) components, oxidative stress, and insulin pathway in the liver and gastrocnemius muscle and hepatic steatosis in rats with established MetS. After 7 weeks of high-fat (FAT) or control (CT) diets, rats were treated with cyclodextrin (HPβCD) or HPβCD/Ang-(1-7) in the last 6 weeks. FAT-HPβCD/empty rats showed increased adiposity index and body mass, gene expression of ACE/ANG II/AT1R axis, and oxidative stress. These results were accompanied by imbalances in the insulin pathway, worsening of liver function, hyperglycemia, and dyslipidemia. Oral HPβCD/Ang-(1-7) treatment decreased ACE and AT1R, increased ACE2 gene expression in the liver, and restored thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), insulin receptor substrate (Irs-1), glucose transporter type 4 (GLUT4), and serine/threonine kinase 2 (AKT-2) gene expression in the liver and gastrocnemius muscle improving hepatic function, cholesterol levels, and hyperglycemia in MetS rats. Overall, HPβCD/Ang-(1-7) treatment restored the RAS components, oxidative stress, and insulin signaling in the liver and gastrocnemius muscle contributing to the establishment of blood glucose and lipid homeostasis in MetS rats.