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Abstract

Non-alcoholic steatohepatitis (NASH) is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6) has been implicated in the pathogenesis of NASH, with the so-called IL-6 ‘trans-signaling’ cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 ‘trans-signaling’, using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice) fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet) and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH.

Item Type:	Article
Authors/Creators:	Kammoun, HL and Allen, TL and Henstridge, DC and Kraakman, MJ and Peijs, L and Rose-John, S and Febbraio, MA
Keywords:	cholesterol, fatty acid, gamma interferon, glycoprotein, interleukin 6, messenger RNA, triacylglycerol, tumor necrosis factor, unclassified drug, biological marker, glycoprotein gp 130, interleukin 6, methionine, body mass
Journal or Publication Title:	PLoS ONE
Publisher:	Public Library of Science
ISSN:	1932-6203
DOI / ID Number:	https://doi.org/10.1371/journal.pone.0179099
Copyright Information:	Copyright 2017 Kammoun et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
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