Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2019; 11(4): 359-369
Published online Apr 27, 2019. doi: 10.4254/wjh.v11.i4.359
Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model
Francielle Graus-Nunes, Felipe de Oliveira Santos, Thatiany de Souza Marinho, Carolline Santos Miranda, Sandra Barbosa-da-Silva, Vanessa Souza-Mello
Francielle Graus-Nunes, Felipe de Oliveira Santos, Thatiany de Souza Marinho, Carolline Santos Miranda, Sandra Barbosa-da-Silva, Vanessa Souza-Mello, Laboratório de Morfometria, Metabolismo e Doenças Cardiovasculares, Departamento de Anatomia, Instituto de Biologia Roberto Alcântara Gomes, Rio de Janeiro 20551-030, Brazil
Author contributions: Graus-Nunes F performed the majority of experiments and analyzed the data; Santos FO, Marinho TS and Miranda CS performed the molecular investigations; Graus-Nunes F, Oliveira FO, Marinho TS and Miranda CS participated equally in the handling of animals; Graus-Nunes F, Barbosa-da-Silva S and Souza-Mello V designed and coordinated the research; Graus-Nunes F, Oliveira FO and Souza-Mello V wrote the paper.
Supported by: Fundação Carlos Chagas Filho de Apoio àPesquisa do Estado do Rio de Janeiro, No. E-26/202.888/2015 for V.S-M.
Institutional review board statement: The study protocol is in line with the National Institute of Health (NIH, publication number 85–23, revised in 1996) and was approved by the Institutional Review (scientific) Board (IBRAG IRB-013/15) of the Institute of Biology Roberto Alcântara Gomes (IBRAG), State University of Rio de Janeiro.
Institutional animal care and use committee statement: The study was approved by the local animal care and use committee, protocol CEUA/013/2015.
Conflict-of-interest statement: None of the authors have a conflict of interest to report.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Vanessa Souza-Mello, Adjunct professor, Laboratório de Morfometria, Metabolismo e Doenças Cardiovasculares, Departamento de Anatomia, Instituto de Biologia Roberto Alcântara Gomes, Av. 28 de setembro 87 fundos, Rio de Janeiro 20551-030, Brazil. souzamello.uerj@gmail.com
Telephone: +55-21-28688689 Fax: +55-21-2868-8033
Received: December 11, 2018
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
Processing time: 136 Days and 3.6 Hours
ARTICLE HIGHLIGHTS
Research background

Drugs that target the renin-angiotensin system (RAS) could benefit the adverse hepatic remodeling and glycemic control in the diet-induced obese mouse.

Research motivation

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.

Research objectives

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.

Research methods

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).

Research results

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.

Research conclusions

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.

Research perspectives

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.