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

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 C57BL/6 mice were randomly divided into two nutritional groups for 10 wk: control group (C, = 5, 10% of energy as fat) or high-fat group (HF, = 15, 50% of energy as fat). After treatment started, the HF group was randomly divided into three groups: untreated HF group ( = 5), HF treated with losartan (HFL, = 5) and HF treated with telmisartan (HFT, = 5). The treatments lasted for 5 wk, and the dose was 10 mg/kg body mass.

Results: HF diet induced body mass gain (+28%, < 0.0001), insulin resistance (+69%, = 0.0079), high hepatic triacylglycerol (+127%, = 0.0004), and overexpression of intrahepatic angiotensin-converting enzyme (ACE) 1/ ANGII type 1 receptor (AT1r) (+569.02% and +141.40%, respectively, < 0.0001). The HFL and HFT groups showed higher ACE2/rMAS gene expression compared to the HF group (ACE2: +465.57%, = 0.0002 for HFL and +345.17%, = 0.0049 for HFT; rMAS: +711.39%, < 0.0001 for HFL and +539.75%, < 0.0001 for HFT), followed by reduced insulin/glucose ratio (-30% for HFL and -33% for HFT, = 0.0181), hepatic triacylglycerol levels (-28%, = 0.0381 for HFL; and -45%, = 0.0010 for HFT, and Plin2 expression.

Conclusion: Modulation 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.