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Lookup NU author(s): Professor Chris Day,
Professor Alastair BurtORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019, The Author(s). Non-alcoholic fatty liver disease (NAFLD) is often associated with obesity and type 2 diabetes. To disentangle etiological relationships between these conditions and identify genetically-determined metabolites involved in NAFLD processes, we mapped 1 H nuclear magnetic resonance (NMR) metabolomic and disease-related phenotypes in a mouse F2 cross derived from strains showing resistance (BALB/c) and increased susceptibility (129S6) to these diseases. Quantitative trait locus (QTL) analysis based on single nucleotide polymorphism (SNP) genotypes identified diet responsive QTLs in F2 mice fed control or high fat diet (HFD). In HFD fed F2 mice we mapped on chromosome 18 a QTL regulating liver micro- and macrovesicular steatosis and inflammation, independently from glucose intolerance and adiposity, which was linked to chromosome 4. Linkage analysis of liver metabolomic profiling data identified a QTL for octopamine, which co-localised with the QTL for liver histopathology in the cross. Functional relationship between these two QTLs was validated in vivo in mice chronically treated with octopamine, which exhibited reduction in liver histopathology and metabolic benefits, underlining its role as a mechanistic biomarker of fatty liver with potential therapeutic applications.
Author(s): Brial F, Le Lay A, Hedjazi L, Tsang T, Fearnside JF, Otto GW, Alzaid F, Wilder SP, Venteclef N, Cazier J-B, Nicholson JK, Day C, Burt AD, Gut IG, Lathrop M, Dumas M-E, Gauguier D
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Online publication date: 06/03/2019
Acceptance date: 17/01/2019
Date deposited: 20/03/2019
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
PubMed id: 30842494
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