Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model  

作　　者：Francielle Graus-Nunes Felipe de Oliveira Santos Thatiany de Souza Marinho Carolline Santos Miranda Sandra Barbosa-da-Silva Vanessa Souza-Mello 

机构地区：[1]Laboratorio de Morfometria,Metabolismo e Doencas Cardiovasculares, Departamento de Anatomia, Instituto de Biologia Roberto Alcantara Gomes

出　　处：《World Journal of Hepatology》2019年第4期359-369,共11页世界肝病学杂志（英文版）（电子版）

基　　金：Fundacao Carlos Chagas Filho de Apoio aPesquisa do Estado do Rio de Janeiro,No.E-26/202.888/2015 for V.S-M

摘　　要：BACKGROUND Obesity has been associated with hepatic overexpression of the renin-angiotensin system(RAS).AIM To evaluate the action of two angiotensin II(ANGII) receptor blockers(losartan or telmisartan) on the modulation of local hepatic RAS and the resulting metabolic effects in a diet-induced obesity murine model.METHODS Twenty C57 BL/6 mice were randomly divided into two nutritional groups for 10 wk: control group(C, n = 5, 10% of energy as fat) or high-fat group(HF, n = 15,50% of energy as fat). After treatment started, the HF group was randomly divided into three groups: untreated HF group(n = 5), HF treated with losartan(HFL, n = 5) and HF treated with telmisartan(HFT, n = 5). The treatments lasted for 5 wk, and the dose was 10 mg/kg body mass.RESULTS HF diet induced body mass gain(+28%, P < 0.0001), insulin resistance(+69%, P =0.0079), high hepatic triacylglycerol(+127%, P = 0.0004), and overexpression of intrahepatic angiotensin-converting enzyme(ACE) 1/ANGII type 1 receptor(AT1 r)(+569.02% and +141.40%, respectively, P < 0.0001). The HFL and HFT groups showed higher ACE2/rMAS gene expression compared to the HF group(ACE2: +465.57%, P = 0.0002 for HFL and +345.17%, P = 0.0049 for HFT; rMAS:+711.39%, P < 0.0001 for HFL and +539.75%, P < 0.0001 for HFT), followed by reduced insulin/glucose ratio(-30% for HFL and-33% for HFT, P = 0.0181),hepatic triacylglycerol levels(-28%, P = 0.0381 for HFL; and-45%, P = 0.0010 for HFT, and Plin2 expression.CONCLUSION Modulation of the intrahepatic RAS, with favored involvement of the ACE2/rMAS axis over the ACE1/AT1 r axis after losartan or telmisartan treatments, caused hepatic and metabolic beneficial effects as demonstrated by reduced hepatic triacylglycerol levels coupled with reduced PLIN 2 expression and improved glycemic control.BACKGROUND Obesity has been associated with hepatic overexpression of the renin-angiotensin system(RAS).AIM To evaluate the action of two angiotensin II(ANGII) receptor blockers(losartan or telmisartan) on the modulation of local hepatic RAS and the resulting metabolic effects in a diet-induced obesity murine model.METHODS Twenty C57 BL/6 mice were randomly divided into two nutritional groups for 10 wk: control group(C, n = 5, 10% of energy as fat) or high-fat group(HF, n = 15,50% of energy as fat). After treatment started, the HF group was randomly divided into three groups: untreated HF group(n = 5), HF treated with losartan(HFL, n = 5) and HF treated with telmisartan(HFT, n = 5). The treatments lasted for 5 wk, and the dose was 10 mg/kg body mass.RESULTS HF diet induced body mass gain(+28%, P < 0.0001), insulin resistance(+69%, P =0.0079), high hepatic triacylglycerol(+127%, P = 0.0004), and overexpression of intrahepatic angiotensin-converting enzyme(ACE) 1/ANGII type 1 receptor(AT1 r)(+569.02% and +141.40%, respectively, P < 0.0001). The HFL and HFT groups showed higher ACE2/rMAS gene expression compared to the HF group(ACE2: +465.57%, P = 0.0002 for HFL and +345.17%, P = 0.0049 for HFT; rMAS:+711.39%, P < 0.0001 for HFL and +539.75%, P < 0.0001 for HFT), followed by reduced insulin/glucose ratio(-30% for HFL and-33% for HFT, P = 0.0181),hepatic triacylglycerol levels(-28%, P = 0.0381 for HFL; and-45%, P = 0.0010 for HFT, and Plin2 expression.CONCLUSION Modulation of the intrahepatic RAS, with favored involvement of the ACE2/rMAS axis over the ACE1/AT1 r axis after losartan or telmisartan treatments, caused hepatic and metabolic beneficial effects as demonstrated by reduced hepatic triacylglycerol levels coupled with reduced PLIN 2 expression and improved glycemic control.

关 键 词：Liver TELMISARTAN LOSARTAN OBESITY Angiotensin Ⅱ type 1 receptor C57BL/6 mouse 

分 类 号：R[医药卫生]