Journal article
Systems genetics of Hepatic Metabolome Reveals Octopamine as a Target for Non-Alcoholic Fatty Liver Disease Treatment
Scientific Reports, Vol.9(1)
2019
Abstract
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 1H 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.
Details
- Title
- Systems genetics of Hepatic Metabolome Reveals Octopamine as a Target for Non-Alcoholic Fatty Liver Disease Treatment
- Authors/Creators
- F. Brial (Author/Creator) - Délégation Paris 7A. Le Lay (Author/Creator) - Délégation Paris 7L. Hedjazi (Author/Creator) - Délégation Paris 7T. Tsang (Author/Creator) - Imperial College LondonJ.F. Fearnside (Author/Creator) - University of SheffieldG.W. Otto (Author/Creator) - UCL Institute of Child HealthF. Alzaid (Author/Creator) - Délégation Paris 7S.P. Wilder (Author/Creator) - Centre for Human GeneticsN. Venteclef (Author/Creator) - Délégation Paris 7J-B Cazier (Author/Creator) - University of BirminghamJ.K. Nicholson (Author/Creator) - Imperial College LondonC. Day (Author/Creator) - Faculty (United Kingdom)A.D. Burt (Author/Creator) - The University of AdelaideI.G. Gut (Author/Creator) - Centre for Genomic RegulationM. Lathrop (Author/Creator) - McGill University and Génome Québec Innovation CentreM-E Dumas (Author/Creator) - Imperial College LondonD. Gauguier (Author/Creator) - Délégation Paris 7
- Publication Details
- Scientific Reports, Vol.9(1)
- Publisher
- Springer Nature
- Identifiers
- 991005545019007891
- Copyright
- © 2019 The Author(s)
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.125 Hepatitis
- 1.125.663 NAFLD
- Web Of Science research areas
- Multidisciplinary Sciences
- ESI research areas
- Clinical Medicine