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Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice

Citation

Kammoun, HL and Allen, TL and Henstridge, DC and Kraakman, MJ and Peijs, L and Rose-John, S and Febbraio, MA, Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice, PLoS ONE, 12, (6) pp. e0179099. ISSN 1932-6203 (2017) [Refereed Article]


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Copyright 2017 Kammoun et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1371/journal.pone.0179099

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 Details

Item Type:Refereed Article
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
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Metabolism
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Diabetes
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133370
Year Published:2017
Web of Science® Times Cited:3
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-10
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