Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Sep 8, 2015; 7(19): 2184-2188
Published online Sep 8, 2015. doi: 10.4254/wjh.v7.i19.2184
Targeting Kupffer cells in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Why and how?
Nicolas Lanthier
Nicolas Lanthier, Service d’Hépato-gastroentérologie, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, 1200 Brussels, Belgium
Nicolas Lanthier, Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200 Brussels, Belgium
Author contributions: Lanthier N performed the research and wrote the paper.
Supported by A grant from the Fund for Scientific Medical Research (Belgium), No. FRS-FNRS CDR J.0100.15.
Conflict-of-interest statement: Nothing to disclose.
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. Nicolas Lanthier, MD, PhD, Service d’Hépatogastroentérologie, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium. nicolas.lanthier@uclouvain.be
Telephone: +32-2-7645275 Fax: +32-2-7645346
Received: May 29, 2015
Peer-review started: May 29, 2015
First decision: June 18, 2015
Revised: July 8, 2015
Accepted: July 23, 2015
Article in press: July 27, 2015
Published online: September 8, 2015
Processing time: 103 Days and 12.2 Hours
Abstract

Mechanisms for non-alcoholic steatohepatitis (NASH) development are under investigation in an era of increased prevalence of obesity and metabolic syndrome. Previous findings have pointed to the role of adipose tissue, adipose tissue macrophages and their secretory products in the development of a chronic inflammatory status inducing insulin resistance and a higher risk of liver steatosis called non-alcoholic fatty liver disease. The activation of resident macrophages [Kupffer cells (KC)] and the recruitment of blood derived monocytes/macrophages into the diseased liver have now been identified as key elements for disease initiation and progression. Those cells could be activated through gut flora modifications and an altered gut barrier function but also through the internalization of toxic lipid compounds in adjacent hepatocytes or in KC themselves. Due to the role of activated KC in insulin resistance, fibrosis development and inflammation amplification, they became a target in clinical trials. A shift towards an anti-inflammatory KC phenotype through peroxisome proliferator activator-receptorδ agonists, an inhibition of macrophage recruitment through anti-C-C chemokine receptor 2 action and a specific blocking of internalization of toxic lipoxidation or glycation compounds into KC by galectin-3 receptor inhibitors are now under investigation in human NASH.

Keywords: Steatosis; Non-alcoholic steatohepatitis; Insulin; Non-alcoholic fatty liver disease; Macrophage

Core tip: Previous findings in the context of obesity have pointed to the role of macrophages from the adipose tissue in the development of a chronic inflammatory status inducing insulin resistance and non-alcoholic fatty liver disease (NAFLD). However, nowadays, the activation of liver macrophages called Kupffer cells (KC) and the recruitment of monocytes have been identified as key elements for disease initiation and progression towards steatohepatitis and cirrhosis. What are the possible reasons for this deleterious KC activation in NAFLD? Are our current therapeutic approaches in NAFLD targeting KC and how? Those two important questions are raised in this paper, supported by recent studies in the field.