MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

Miller, A. M., Gilchrist, D. S., Nijjar, J., Araldi, E., Ramirez, C. M., Lavery, C. A., Fernández-Hernando, C., McInnes, I. B. and Kurowska-Stolarska, M. (2013) MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice. PLoS ONE, 8(8), e72324. (doi:10.1371/journal.pone.0072324) (PMID:23991091) (PMCID:PMC3749101)

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Abstract

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Gilchrist, Dr Derek and Miller, Dr Ashley and Kurowska-Stolarska, Dr Mariola and Nijjar, Dr Jagtar
Authors: Miller, A. M., Gilchrist, D. S., Nijjar, J., Araldi, E., Ramirez, C. M., Lavery, C. A., Fernández-Hernando, C., McInnes, I. B., and Kurowska-Stolarska, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS ONE 8(8):e72324
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
483611Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY
483612Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY