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A low iron diet protects from steatohepatitis in a mouse model


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, A low iron diet protects from steatohepatitis in a mouse model, Nutrients, 11, (9) pp. 1-16. ISSN 2072-6643 (2019) [Refereed Article]


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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

DOI: doi:10.3390/nu11092187


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 Details

Item Type:Refereed Article
Keywords:NAFLD, RNA-seq, iron, metabolic syndrome
Research Division:Biomedical and Clinical Sciences
Research Group:Nutrition and dietetics
Research Field:Nutritional science
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Kavanagh, K (Associate Professor Kylie Kavanagh)
ID Code:144346
Year Published:2019
Web of Science® Times Cited:7
Deposited By:Medicine
Deposited On:2021-05-14
Last Modified:2021-06-23
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