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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2016; 22(36): 8112-8122
Published online Sep 28, 2016. doi: 10.3748/wjg.v22.i36.8112
Iron and non-alcoholic fatty liver disease
Laurence J Britton, V Nathan Subramaniam, Darrell HG Crawford
Laurence J Britton, Darrell HG Crawford, Gallipoli Medical Research Institute, The University of Queensland, Greenslopes Private Hospital, Brisbane, Queensland 4120, Australia
Laurence J Britton, The Princess Alexandra Hospital, Brisbane, Queensland 4120, Australia
V Nathan Subramaniam, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4120, Australia
Author contributions: Britton LJ reviewed the literature and wrote the manuscript; Subramaniam VN and Crawford DHG reviewed the manuscript and made important changes to the content.
Conflict-of-interest statement: No 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: Dr. Laurence J Britton, Gallipoli Medical Research Institute, The University of Queensland, Greenslopes Private Hospital, Newdegate Street, Greenslopes, Brisbane, Queensland 4120, Australia. l.britton@uq.edu.au
Telephone: +61-7-33947284 Fax: +61-7-33947767
Received: March 28, 2016
Peer-review started: April 1, 2016
First decision: May 30, 2016
Revised: July 6, 2016
Accepted: August 5, 2016
Article in press: August 5, 2016
Published online: September 28, 2016
Processing time: 181 Days and 14.5 Hours
Abstract

The mechanisms that promote liver injury in non-alcoholic fatty liver disease (NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis.

Keywords: Iron; Fatty liver; Liver steatosis; Insulin resistance; Steatohepatitis; Diabetes mellitus; Adipose tissue

Core tip: Iron represents a potential therapeutic target for the treatment of non-alcoholic fatty liver disease (NAFLD). There are extensive data that link iron and disease pathogenesis in human studies as well as animal and cell culture models. Studies have predominantly focussed on the role of hepatic iron, although recently adipose tissue has emerged as a site at which iron may promote insulin resistance. In this review, we summarize the human and basic science data that have evaluated the role of iron in NAFLD pathogenesis.