Imperial College London
Alternate

ProfessorElaineHolmes

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3220elaine.holmes

 
 
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Location

 

661Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Toye:2007:10.1007/s00125-007-0738-5,
author = {Toye, AA and Dumas, ME and Blancher, C and Rothwell, AR and Fearnside, JF and Wilder, SP and Bihoreau, MT and Cloarec, O and Azzouzi, I and Young, S and Barton, RH and Holmes, E and McCarthy, MI and Tatoud, R and Nicholson, JK and Scott, J and Gauguier, D},
doi = {10.1007/s00125-007-0738-5},
journal = {Diabetologia},
pages = {1867--1879},
title = {Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice},
url = {http://dx.doi.org/10.1007/s00125-007-0738-5},
volume = {50},
year = {2007}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Aims/hypothesis  Complex changes in gene expression are associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD) promoted by feeding a high-fat diet (HFD). We used functional genomic technologies to document molecular mechanisms associated with diet-induced NAFLD.   Materials and Methods  Male 129S6 mice were fed a diet containing 40% fat (high-fat diet, HFD) for 15 weeks. Glucose tolerance, in vivo insulin secretion, plasma lipid profile and adiposity were determined. Plasma metabonomics and liver transcriptomics were used to identify changes in gene expression associated with HFD-induced NAFLD.   Results  In HFD-fed mice, NAFLD and impaired glucose and lipid homeostasis were associated with increased hepatic transcription of genes involved in fatty acid uptake, intracellular transport, modification and elongation, whilst genes involved in beta-oxidation and lipoprotein secretion were, paradoxically, also upregulated. NAFLD developed despite strong and sustained downregulation of transcription of the gene encoding stearoyl-coenzyme A desaturase 1 (Scd1) and uncoordinated regulation of transcription of Scd1 and the gene encoding sterol regulatory element binding factor 1c (Srebf1c) transcription. Inflammatory mechanisms appeared to be stimulated by HFD.   Conclusions/interpretation  Our results provide an accurate representation of subtle changes in metabolic and gene expression regulation underlying disease-promoting and compensatory mechanisms, collectively contributing to diet-induced insulin resistance and NAFLD. They suggest that proposed models of NAFLD pathogenesis can be enriched with novel diet-reactive genes and disease mechanisms.   Electronic supplementary material  The online version of this article (doi:10.1007/s00125-007-0738-5) contains supplementary material, which is available to authorised users.
AU  - Toye,AA
AU  - Dumas,ME
AU  - Blancher,C
AU  - Rothwell,AR
AU  - Fearnside,JF
AU  - Wilder,SP
AU  - Bihoreau,MT
AU  - Cloarec,O
AU  - Azzouzi,I
AU  - Young,S
AU  - Barton,RH
AU  - Holmes,E
AU  - McCarthy,MI
AU  - Tatoud,R
AU  - Nicholson,JK
AU  - Scott,J
AU  - Gauguier,D
DO  - 10.1007/s00125-007-0738-5
EP  - 1879
PY  - 2007///
SN  - 0012-186X
SP  - 1867
TI  - Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice
T2  - Diabetologia
UR  - http://dx.doi.org/10.1007/s00125-007-0738-5
UR  - http://www.springerlink.com/
VL  - 50
ER  -
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