Santos Sérgio Henrique S, Fernandes Luciana Rodrigues, Pereira Camila Santos, Guimarães André L Senna, de Paula Alfredo M B, Campagnole-Santos Maria José, Alvarez-Leite Jacqueline Isaura, Bader Michael, Santos Robson Augusto S
National Institute of Science and Technology (INCT-NanoBiofar), Physiology Department, Biological Sciences Institute (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
Regul Pept. 2012 Oct 10;178(1-3):64-70. doi: 10.1016/j.regpep.2012.06.009. Epub 2012 Jun 29.
The aim of the present study was to evaluate the effect of a transgenic-induced chronic increase of Ang-(1-7) on the expression of inflammatory markers in adipose tissue and the metabolic profile in rats treated with high-fat diet.
Transgenic rats expressing an Ang-(1-7)-producing fusion protein (TGR L-3292) and Sprague Dawley (SD) control rats 4 weeks old were treated for 8 weeks with a high-fat diet. Food intake and body weight were measured once a week. Glucose-tolerance and insulin sensitivity tests were performed one week before the sacrifice. At the end of the experiment plasma lipid concentrations were measured in TGR and SD rats. Adipose tissue were weighted and corrected by the body weight. Proinflammatory markers in adipose tissue were analyzed using Western-blotting, real time-PCR and immunohistochemistry.
High-fat diet TGR rats presented increased HDL cholesterol levels and decreased abdominal fat mass, without changes in food intake. In addition, rats with increased Ang-(1-7) levels had lower body weight. Molecular analysis revealed decreased IL-1β and COX-2 in adipose tissue.
Taken together, these results show that chronic high circulating angiotensin-(1-7) levels protect against metabolic stress induced by a high-fat diet decreasing the proinflammatory profile of adipose tissue.
本研究的目的是评估转基因诱导的血管紧张素-(1-7)慢性增加对高脂饮食处理的大鼠脂肪组织中炎症标志物表达和代谢谱的影响。
将4周龄表达产生血管紧张素-(1-7)融合蛋白的转基因大鼠(TGR L-3292)和Sprague Dawley(SD)对照大鼠用高脂饮食处理8周。每周测量一次食物摄入量和体重。在处死前一周进行葡萄糖耐量和胰岛素敏感性测试。实验结束时,测量TGR和SD大鼠的血浆脂质浓度。称量脂肪组织重量并按体重进行校正。使用蛋白质免疫印迹法、实时聚合酶链反应和免疫组织化学分析脂肪组织中的促炎标志物。
高脂饮食的TGR大鼠高密度脂蛋白胆固醇水平升高,腹部脂肪量减少,食物摄入量无变化。此外,血管紧张素-(1-7)水平升高的大鼠体重较低。分子分析显示脂肪组织中白细胞介素-1β和环氧化酶-2减少。
综上所述,这些结果表明,慢性高循环血管紧张素-(1-7)水平可预防高脂饮食诱导的代谢应激,降低脂肪组织的促炎状态。