Imperial College London

Emeritus ProfessorJeremyNicholson

Faculty of MedicineDepartment 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{Wu:2015:10.1038/ijo.2015.33,
author = {Wu, Q and Li, JV and Seyfried, F and le, Roux CW and Ashrafian, H and Athanasiou, T and Fenske, W and Darzi, A and Nicholson, JK and Holmes, E and Gooderham, NJ},
doi = {10.1038/ijo.2015.33},
journal = {International Journal of Obesity},
pages = {1126--1134},
title = {Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery.},
url = {http://dx.doi.org/10.1038/ijo.2015.33},
volume = {2015},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background/Objectives: Bariatric surgery offers sustained dramatic weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear.Subjects/MethodsWe mapped the co-ordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. Results: The response of circulating miRNAs to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signalling pathways including G protein signalling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, TCA cycle, pentose phosphate shunt, fatty acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. Conclusions: The close association between energy metabolism, neuronal signalling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting.International Journal of Obesity accepted article previe
AU - Wu,Q
AU - Li,JV
AU - Seyfried,F
AU - le,Roux CW
AU - Ashrafian,H
AU - Athanasiou,T
AU - Fenske,W
AU - Darzi,A
AU - Nicholson,JK
AU - Holmes,E
AU - Gooderham,NJ
DO - 10.1038/ijo.2015.33
EP - 1134
PY - 2015///
SN - 1476-5497
SP - 1126
TI - Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery.
T2 - International Journal of Obesity
UR - http://dx.doi.org/10.1038/ijo.2015.33
UR - http://www.ncbi.nlm.nih.gov/pubmed/25783038
UR - http://hdl.handle.net/10044/1/21693
VL - 2015
ER -