Abstract 471: Oral Formulation Of Angiotensin-(1-7) Improves Metabolic Parameters And Insulin-signaling Pathway In Adipose Tissue Of Rats With Metabolic Syndrome
In this study we evaluated the potential therapeutic effect of the oral formulation of angiotensin-(1-7) [Ang-(1-7)] included in cyclodextrin (HPβCD) on biochemical parameters, expression of adipokines and insulin-signaling pathway in the retroperitoneal adipose tissue (rWAT) of rats with metabolic syndrome (MS) induced by high fat diet. Rats were subjected to AIN-93 (CT) or high-fat (MS) diet for 13 weeks. HβCD-Ang-(1-7) or vehicle (V) was given in the last 6 weeks by gavage. MS-V rats presented increased body weight (314±10 vs 283±6 g, CT), adipositivity index (8±0.3 vs 5±0.1, CT), fasting glucose plasma levels (7±0.1 vs 6±0.1 mmol/L, CT), total cholesterol (2.0±0.1 vs 1.7±0.03 mmol/L, CT) and increased alanine aminotransferase (ALT; 65±2 vs 57±2 a.u., CT). In addition, there was an increase in mRNA levels (a.u.) of adipokines, leptin (18±6 vs 5±3), resistin (10±3 vs 3±0.9), adipisina (35±10 vs 13±3), TNF-α (0.05±0.01 vs 0.01±0.002) and COX-2 associated to a decrease in the mRNA expression of adiponectin (34±5 vs 89±11), insulin receptor (Irs; 0.3±0.04 vs 0.8±0.1), Irs-1 (0.5±0.1 vs 1.4±0.04), Irs-2 (0.2±0.03 vs 0.6±0.1), Akt-2 (2±0.6 vs 4±0,3) and GLUT-4 (0.2±0.03 vs 0.5±0.01) in the rWAT of MS rats. However, MS rats treated with HβCD-Ang-(1-7) presented reduction in body weight, adiposity index (7 ± 03), in fasting glucose plasma levels (7±0.1 mmol/L), total cholesterol and ALT mRNA (58±2 a.u.) compared to MS untreated rats. HβCD-Ang-(1-7) treatment also induced a decrease in the mRNA expression (a.u.) of leptin (6±11), resistin (2±0.4), adipisina (9±1), TNF-α (0.008±0.0006) and COX-2 and increase in Irs-1(0.73±0.1), Irs-2 (0.3±0.09) and GLUT-4 (0.34±0.03) in rWAT compared to MS-V rats. Our data showed that treatment with HβCD-Ang-(1-7) reversed the changes in metabolic and biometrics parameters, reduced the expression of pro-inflammatory adipokines and improved the insulin-signaling pathway in the rWAT of rats with MS induced by high-fat diet.
Author Disclosures: R.A.S. Santos: None. U.G.M. de Castro: None. R. Guerra: None. M.A. Barbosa: None. K.B. Queiroz: None. R.C. Nicolato: None. M. Silva: None. M.J. Campagnole-Santos: None. A.C. Alzamora: None.
- © 2014 by American Heart Association, Inc.