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

In prevention studies of metabolic syndrome (MetS), Ang-(1-7) has shown to improve the insulin signaling. We evaluated the HPCD/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 (HPCD) or HPCD/Ang-(1-7) in the last 6 weeks. FAT-HPCD/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 HPCD/Ang-(1-7) treatment decreased and , increased gene expression in the liver, and restored thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), insulin receptor substrate (), glucose transporter type 4 (), and serine/threonine kinase 2 () gene expression in the liver and gastrocnemius muscle improving hepatic function, cholesterol levels, and hyperglycemia in MetS rats. Overall, HPCD/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.