Published online Apr 27, 2019. doi: 10.4254/wjh.v11.i4.359
Peer-review started: December 11, 2018
First decision: January 27, 2019
Revised: February 23, 2019
Accepted: March 16, 2019
Article in press: March 16, 2019
Published online: April 27, 2019
Drugs that target the renin-angiotensin system (RAS) could benefit the adverse hepatic remodeling and glycemic control in the diet-induced obese mouse.
Most obese subjects show insulin resistance and non-alcoholic fatty liver disease (often referred to as NAFLD), whose consequences lead to high healthcare costs. Currently, there is no established drug treatment for NAFLD.
To evaluate the action of losartan or telmisartan on the modulation of intrahepatic RAS and the resulting metabolic effects in a diet-induced obesity murine model.
Twenty C57BL/6 mice were randomly divided into two nutritional groups for 10 wk and, then, into four groups for a 5-wk treatment: control group (C, n = 5), high-fat group (HF, n = 15), HF treated with losartan (HFL, n = 5, 10 mg/kg body mass) and HF treated with telmisartan (HFT, n = 5, 10 mg/kg body mass).
The HF group showed increased weight, glucose intolerance, high hepatic triacylglycerol, and overexpression of intrahepatic angiotensin-converting enzyme (ACE) 1/ angiotensin II (ANGII) type 1 receptor (AT1r). Losartan and telmisartan modulated the intrahepatic RAS, with preference for the ACE2/rMAS axis, resulting in ameliorated glucose intolerance and reduced hepatic triacylglycerol levels, both of which are related to diminished Plin2 expression in the liver. Only telmisartan could restore body mass, fasting glucose levels, and hepatic cholesterol levels, implying additional benefits.
The modulation of intrahepatic RAS, with preference for 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.
The pharmacological modulation of intrahepatic RAS showed beneficial effects in terms of hepatic steatosis, evaluated by reduced hepatic triacylglycerol levels, in addition to its effects on decreased body mass and better glycemic control. These drugs could be a viable option to treat NAFLD in obese and/or hypertensive patients.