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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Myeloid cell deletion of Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) induces non-alcoholic steatohepatitis
PLoS ONE, Volume 14, No. 12, Article e0225332, Year 2019
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Description
Background and aim Non-alcoholic steatohepatitis (NASH) is predicted to become the most common cause of cirrhosis and liver failure. Risk factors include obesity, insulin resistance and diabetes. Macrophages and other myeloid cells play crucial roles in initiating and driving inflammation. Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) is a transcription factor which binds to a range of partners to mediate responses to environmental signals, including the diet. In people with diabetes it is decreased in liver. We hypothesised that myeloid cell ARNT activity may contribute to the development of liver pathology. Methods Floxed-ARNT mice were bred with LysM-Cre mice to generate mice with reduced ARNT in myeloid cells. Animals were fed a high fat diet (HFD) and liver pathology was assessed. Histology, mRNA, fat accumulation and metabolism were studied. Results Animals with reduced myeloid ARNT developed steatohepatitis on a HFD, with additional alterations of metabolism and fat deposition. Steatohepatitis was accompanied by hepatic macrophage infiltration and expression of both M1 and M2 markers. Expression of mRNAs for Cxcl1, Mcp-1, Tnf-α and Tgf-β1 were increased. Human livers from controls and people with NASH were tested; ARNT mRNA was decreased by 80% (p = 0.0004). Conclusions Decreased myeloid ARNT may play a role in the conversion from non-alcoholic fatty liver to steatohepatitis. Increasing ARNT may be a therapeutic strategy to reduce NASH. © 2019 Scott et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Authors & Co-Authors
Eslam, Mohammed
Australia, Sydney
The University of Sydney
Australia, Parramatta
The Westmead Institute for Medical Research
Metwally, Mayada
Australia, Sydney
The University of Sydney
Australia, Parramatta
The Westmead Institute for Medical Research
George, Jacob A.
Australia, Sydney
The University of Sydney
Australia, Parramatta
The Westmead Institute for Medical Research
Gunton, Jenny E.
Australia, Parramatta
The Westmead Institute for Medical Research
Australia, Sydney
The University of Sydney
Australia, Sydney
Garvan Institute of Medical Research
Australia, Sydney
St. Vincent's Hospital Sydney
Statistics
Citations: 6
Authors: 4
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pone.0225332
ISSN:
19326203
Research Areas
Cancer
Health System And Policy
Noncommunicable Diseases