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A low iron diet protects from steatohepatitis in a mouse model

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Salaye, L, Bychkova, I, Sink, S, Kovalic, AJ, Bharadwaj, MS, Lorenzo, F, Jain, S, Harrison, AV, Davis, AT, Turnbull, K, Meegalla, NT, Lee, SH, Cooksey, R, Donati, GL, Kavanagh, K, Bonkovsky, HL and McClain, DA 2019 , 'A low iron diet protects from steatohepatitis in a mouse model' , Nutrients, vol. 11, no. 9 , pp. 1-16 , doi: 10.3390/nu11092187.

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Abstract

High tissue iron levels are a risk factor for multiple chronic diseases including type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). To investigate causal relationships and underlying mechanisms, we used an established NAFLD model-mice fed a high fat diet with supplemental fructose in the water ("fast food", FF). Iron did not affect excess hepatic triglyceride accumulation in the mice on FF, and FF did not affect iron accumulation compared to normal chow. Mice on low iron are protected from worsening of markers for non-alcoholic steatohepatitis (NASH), including serum transaminases and fibrotic gene transcript levels. These occurred prior to the onset of significant insulin resistance or changes in adipokines. Transcriptome sequencing revealed the major effects of iron to be on signaling by the transforming growth factor beta (TGF-β) pathway, a known mechanistic factor in NASH. High iron increased fibrotic gene expression in vitro, demonstrating that the effect of dietary iron on NASH is direct. Conclusion: A lower tissue iron level prevents accelerated progression of NAFLD to NASH, suggesting a possible therapeutic strategy in humans with the disease.

Item Type: Article
Authors/Creators:Salaye, L and Bychkova, I and Sink, S and Kovalic, AJ and Bharadwaj, MS and Lorenzo, F and Jain, S and Harrison, AV and Davis, AT and Turnbull, K and Meegalla, NT and Lee, SH and Cooksey, R and Donati, GL and Kavanagh, K and Bonkovsky, HL and McClain, DA
Keywords: NAFLD, RNA-seq, iron, metabolic syndrome
Journal or Publication Title: Nutrients
Publisher: MDPI Publishing
ISSN: 2072-6643
DOI / ID Number: 10.3390/nu11092187
Copyright Information:

Copyright 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license http://creativecommons.org/licenses/by/4.0/).

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