Imperial College London
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ProfessorJulianGriffin

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3220julian.griffin

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sowton:2020:10.1016/j.ymgmr.2020.100580,
author = {Sowton, AP and Padmanabhan, N and Tunster, SJ and McNally, BD and Murgia, A and Yusuf, A and Griffin, JL and Murray, AJ and Watson, ED},
doi = {10.1016/j.ymgmr.2020.100580},
journal = {Molecular Genetics and Metabolism Reports},
pages = {1--10},
title = {Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice},
url = {http://dx.doi.org/10.1016/j.ymgmr.2020.100580},
volume = {23},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Nonalcoholic fatty liver disease (NAFLD) is associated with dietary folate deficiency and mutations in genes required for onecarbon metabolism. However, the mechanism through which this occurs is unclear. To improve our understanding of this link, we investigated liver morphology, metabolism and fuel storage in adult mice with a hypomorphic mutation in the gene methionine synthase reductase (Mtrrgt). MTRR enzyme is a key regulator of the methionine and folate cycles. The Mtrrgt mutation in mice was previously shown to disrupt onecarbon metabolism and cause a wide-spectrum of developmental phenotypes and late adult-onset macrocytic anaemia. Here, we showed that livers of Mtrrgt/gt female mice were enlarged compared to control C57Bl/6J livers. Histological analysis of these livers revealed eosinophilic hepatocytes with decreased glycogen content, which was associated with down-regulation of genes involved in glycogen synthesis (e.g., Ugp2 and Gsk3a genes). While female Mtrrgt/gt livers showed evidence of reduced β-oxidation of fatty acids, there were no other associated changes in the lipidome in female or male Mtrrgt/gt livers compared with controls. Defects in glycogen storage and lipid metabolism often associate with disruption of mitochondrial electron transfer system activity. However, defects in mitochondrial function were not detected in Mtrrgt/gt livers as determined by high-resolution respirometry analysis. Overall, we demonstrated that adult Mtrrgt/gt female mice showed abnormal liver morphology that differed from the NAFLD phenotype and that was accompanied by subtle changes in their hepatic metabolism and fuel storage.
AU  - Sowton,AP
AU  - Padmanabhan,N
AU  - Tunster,SJ
AU  - McNally,BD
AU  - Murgia,A
AU  - Yusuf,A
AU  - Griffin,JL
AU  - Murray,AJ
AU  - Watson,ED
DO  - 10.1016/j.ymgmr.2020.100580
EP  - 10
PY  - 2020///
SN  - 2214-4269
SP  - 1
TI  - Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice
T2  - Molecular Genetics and Metabolism Reports
UR  - http://dx.doi.org/10.1016/j.ymgmr.2020.100580
UR  - https://www.sciencedirect.com/science/article/pii/S2214426920300264?via%3Dihub
UR  - http://hdl.handle.net/10044/1/82233
VL  - 23
ER  -
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