Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model
Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model
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DOI：
10.4254/wjh.v11.i4.359
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发表时间：
2019-04-27
影响因子：
2.4
通讯作者：
Souza-Mello, Vanessa
中科院分区：
文献类型：
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作者：
Graus-Nunes, Francielle;Santos, Felipe de Oliveira;Souza-Mello, Vanessa
背景肥胖与肝脏肾素-血管紧张素系统(RAS)的过度表达有关。目的探讨两种血管紧张素II受体阻滞剂(氯沙坦或替米沙坦)对饮食诱导肥胖小鼠肝脏RAS的调节作用及其代谢效应。方法将C57BL/6小鼠随机分为两组：对照组(C组，10%能量脂肪)和高脂组(HF，n=15，能量50%脂肪)。治疗开始后，心力衰竭组被随机分为3组：未治疗心力衰竭组(n=5)、心力衰竭加用氯沙坦组(n=5)、心力衰竭加替米沙坦组(n=5)。结果大鼠体重增加(+569.02%，P<141.40)，胰岛素抵抗(+69%，P=0.0079)，肝脏血管紧张素转换酶(ACE1)/血管紧张素Ⅱ1型受体(AT1r)表达增加(+141.40%，P=0.0004)，胰岛素抵抗(+69%，P=0.0004)。高频组和高频组ACE2/RMAS基因表达水平明显高于心衰组(ACE2：+465.57%，P=0.0002和+345.17%，P=0.0049；RMAS：+711.39%，P=0.0001和+539.75%，P=0.0001)，胰岛素/血糖比值降低(-30%和-33%，P=0.0181)，肝三酰甘油水平(-28%，P=0.0381)；结论在氯沙坦或替米沙坦治疗后，肝内RAS的调节有利于ACE2/RMAS轴相对于ACE1/AT1R轴的参与，从而导致肝脏和代谢的有益影响，表现为肝脏三酰甘油水平降低，Plin 2表达减少，血糖控制改善。
BACKGROUNDObesity has been associated with hepatic overexpression of the renin-angiotensin system (RAS).AIMTo 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.METHODSTwenty C57BL/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.RESULTSHF 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 (AT1r) (+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.CONCLUSIONModulation of the intrahepatic RAS, with favored involvement of the ACE2/rMAS axis over the ACE1/AT1r 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.