Imperial College London
Alternate

Emeritus ProfessorJeremyNicholson

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Emeritus Professor of Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 3195j.nicholson Website

 
 
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Assistant

 

Ms Wendy Torto +44 (0)20 7594 3225

 
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Location

 

Office no. 665Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Brial:2019:10.1038/s41598-019-40153-0,
author = {Brial, F and Le, Lay A and Hedjazi, L and Tsang, T and Fearnside, JF and Otto, GW and Alzaid, F and Wilder, SP and Venteclef, N and Cazier, J-B and Nicholson, JK and Day, C and Burt, AD and Gut, IG and Lathrop, M and Dumas, M-E and Gauguier, D},
doi = {10.1038/s41598-019-40153-0},
journal = {Scientific Reports},
title = {Systems genetics of hepatic metabolome reveals octopamine as a target for non-alcoholic fatty liver disease treatment},
url = {http://dx.doi.org/10.1038/s41598-019-40153-0},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Brial,F
AU  - Le,Lay A
AU  - Hedjazi,L
AU  - Tsang,T
AU  - Fearnside,JF
AU  - Otto,GW
AU  - Alzaid,F
AU  - Wilder,SP
AU  - Venteclef,N
AU  - Cazier,J-B
AU  - Nicholson,JK
AU  - Day,C
AU  - Burt,AD
AU  - Gut,IG
AU  - Lathrop,M
AU  - Dumas,M-E
AU  - Gauguier,D
DO  - 10.1038/s41598-019-40153-0
PY  - 2019///
SN  - 2045-2322
TI  - Systems genetics of hepatic metabolome reveals octopamine as a target for non-alcoholic fatty liver disease treatment
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-40153-0
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30842494
UR  - http://hdl.handle.net/10044/1/67866
VL  - 9
ER  -
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