Imperial College London
Alternate

ProfessorJulianWalters

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Gastroenterology
 
 
 
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Contact

 

+44 (0)20 3313 2361julian.walters

 
 
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Location

 

Rm368, Hammersmith HouseHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lee:2018:10.1194/jlr.M078279,
author = {Lee, JM and Ong, JR and Vergnes, L and de, Aguiar Vallim TQ and Nolan, J and Cantor, RM and Walters, JRF and Reue, K},
doi = {10.1194/jlr.M078279},
journal = {Journal of Lipid Research},
pages = {429--438},
title = {Diet1, bile acid diarrhea, and FGF15/19: mouse model and human genetic variants},
url = {http://dx.doi.org/10.1194/jlr.M078279},
volume = {59},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Diet1 modulates intestinal production of the hormone fibroblast growth factor 15 (FGF15), which signals in liver to regulate bile acid synthesis. C57BL/6ByJ mice with a spontaneous Diet1 null mutation are resistant to hypercholesterolemia compared to wild-type C57BL/6J mice through enhanced cholesterol conversion to bile acids. To further characterize the role of Diet1 in metabolism, we generated Diet1-/- mice on the C57BL6/J genetic background. C57BL/6J Diet1-/- mice had elevated bile acid levels, reduced Fgf15 expression, and increased gastrointestinal motility and intestinal luminal water content, which are symptoms of bile acid diarrhea (BAD) in humans. Natural genetic variation in Diet1 mRNA expression levels across 76 inbred mouse strains correlated positively with Ffg15 mRNA and negatively with serum bile acid levels. This led us to investigate the role of DIET1 genetic variation in primary BAD patients. We identified a DIET1 coding variant (rs12256835) that had skewed prevalence between BAD cases and controls. This variant causes an H1721Q amino acid substitution that increases the levels of FGF19 protein secreted from cultured cells. We propose that genetic variation in DIET1 may be a determinant of FGF19 secretion levels, and may affect bile acid metabolism in both physiological and pathological conditions.
AU  - Lee,JM
AU  - Ong,JR
AU  - Vergnes,L
AU  - de,Aguiar Vallim TQ
AU  - Nolan,J
AU  - Cantor,RM
AU  - Walters,JRF
AU  - Reue,K
DO  - 10.1194/jlr.M078279
EP  - 438
PY  - 2018///
SN  - 0022-2275
SP  - 429
TI  - Diet1, bile acid diarrhea, and FGF15/19: mouse model and human genetic variants
T2  - Journal of Lipid Research
UR  - http://dx.doi.org/10.1194/jlr.M078279
UR  - http://hdl.handle.net/10044/1/56154
VL  - 59
ER  -
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