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

Abstract

In prevention studies of metabolic syndrome (MetS), Ang-(1-7) has shown to improve the insulin signaling. We evaluated the HP<i>β</i>CD/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 (HP<i>β</i>CD) or HP<i>β</i>CD/Ang-(1-7) in the last 6 weeks. FAT-HP<i>β</i>CD/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 HP<i>β</i>CD/Ang-(1-7) treatment decreased <i>ACE</i> and <i>AT1R</i>, increased <i>ACE2</i> gene expression in the liver, and restored thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), insulin receptor substrate (<i>Irs-1</i>), glucose transporter type 4 (<i>GLUT4</i>), and serine/threonine kinase 2 (<i>AKT-2</i>) gene expression in the liver and gastrocnemius muscle improving hepatic function, cholesterol levels, and hyperglycemia in MetS rats. Overall, HP<i>β</i>CD/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.