Editorial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 18, 2017; 9(2): 74-79
Published online Jan 18, 2017. doi: 10.4254/wjh.v9.i2.74
Hepatic structural enhancement and insulin resistance amelioration due to AT1 receptor blockade
Vanessa Souza-Mello
Vanessa Souza-Mello, Biomedical Centre, Institute of Biology, Department of Anatomy, State University of Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Author contributions: Souza-Mello V solely contributed to this paper.
Conflict-of-interest statement: The author discloses any conflict of interest.
Open-Access: This article is an open-access article which 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/
Correspondence to: Vanessa Souza-Mello, RD, PhD, Biomedical Centre, Institute of Biology, Department of Anatomy, State University of Rio de Janeiro, Av. 28 de Setembro 87, Fundos, Vila Isabel, Rio de Janeiro 20551-030, Brazil. souzamello.uerj@gmail.com
Telephone: +55-21-28688689 Fax: +55-21-28688033
Received: August 27, 2016
Peer-review started: August 29, 2016
First decision: September 27, 2016
Revised: October 27, 2016
Accepted: November 21, 2016
Article in press: November 22, 2016
Published online: January 18, 2017
Abstract

Over the last decade, the role of renin-angiotensin system (RAS) on the development of obesity and its comorbidities has been extensively addressed. Both circulating and local RAS components are up-regulated in obesity and involved in non-alcoholic fatty liver disease onset. Pharmacological manipulations of RAS are viable strategies to tackle metabolic impairments caused by the excessive body fat mass. Renin inhibitors rescue insulin resistance, but do not have marked effects on hepatic steatosis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) yield beneficial hepatic remodeling. ARBs elicit body mass loss and normalize insulin levels, tackling insulin resistance. Also, this drug class increases adiponectin levels, besides countering interleukin-6, tumoral necrosis factor-alpha, and transforming growth factor-beta 1. The latter is essential to prevent from liver fibrosis. When conjugated with peroxisome proliferator-activated receptor (PPAR)-alpha activation, ARB fully rescues fatty liver. These effects might be orchestrated by an indirect up-regulation of MAS receptor due to angiotensin II receptor type 1 (AT1R) blockade. These associations of ARB with PPAR activation and ACE2-angiotensin (ANG) (1-7)-MAS receptor axis deserve a better understanding. This editorial provides a brief overview of the current knowledge regarding AT1R blockade effects on sensitivity to insulin and hepatic structural alterations as well as the intersections of AT1R blockade with peroxisome proliferator-activated receptor activation and ACE2-ANG (1-7) - MAS receptor axis.

Keywords: Non-alcoholic fatty liver disease, Insulin resistance, Angiotensin receptor blockers, MAS receptor, Renin-angiotensin system

Core tip: Intrahepatic renin-angiotensin system activation contributes to insulin resistance and non-alcoholic fatty liver disease onset. ANG II interaction with angiotensin II receptor type 1 (AT1R) mediates pro-inflammatory and pro-fibrogenic responses, besides enhancing the oxidative stress, which makes the liver more prone to noxious liver diseases. AT1R blockers mitigate insulin resistance and fatty liver by enhancing beta-oxidation, reducing lipogenesis and controlling inflammation. The impact of the AT1R blockade on liver ACE2-angiotensin (1-7)-MAS receptor axis remains to be fully unraveled.