Published online Jan 18, 2017. doi: 10.4254/wjh.v9.i2.74
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
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.
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.