Oral Ang-(1-7) treatment improves white adipose tissue remodeling and hypertension in rats with metabolic syndrome

Abstract

ObjectiveAngiotensin (Ang)-(1-7) has preventive effects on metabolic syndrome (MetS). The aim of this study was to evaluate the therapeutic effect of oral Ang-(1-7) on mean arterial pressure (MAP), insulin resistance (IR), inflammatory process, and remodeling of white adipose tissue (WAT) in rats with established MetS. MethodsRats were subjected to control (CT; AIN-93M) or high-fat (HF) diets for 13 wk to induce MetS and treated with Ang-(1-7) or vehicle (V) for the last 6 wk. At the end of 13 wk, MAP, biochemical and histological parameters, and uncoupling protein (UCP) and inflammatory gene expression were determined by quantitative reverse transcription polymerase chain reaction. ResultsHF-V rats showed increased visceral fat deposition, inflammatory cytokine expression, hyperplasia, and hypertrophy in retroperitoneal (WAT) and brown adipose tissue (BAT). Additionally, the gastrocnemius muscle reduced UCP-3 and increased the UCP-1 expression in BAT. HF-V also elevated levels of plasma insulin, glucose, homeostatic model assessment (HOMA) of IR and HOMA-β, and increased body mass, adiposity, and MAP. Ang-(1-7) treatment in rats with MetS [HF-Ang-(1-7)] reduced WAT area, number of adipocytes, and expression of proinflammatory adipokines in WAT and BAT and increased UCP-3 in gastrocnemius muscle and UCP-1 expression in BAT compared with the HF-V group. These events prevented body mass gain, reduced adiposity, and normalized fasting plasma glucose, insulin levels, HOMA-IR, HOMA-β, and MAP. ConclusionData from the present study demonstrated that oral Ang-(1-7) treatment is effective in restoring biochemical parameters and hypertension in established MetS by improving hypertrophy and hyperplasia in WAT and inflammation in adipose tissue, and regulating metabolic processes in the gastrocnemius muscle and BAT.