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dc.contributor.authorSowton, Alice Pen
dc.contributor.authorPadmanabhan, Nishaen
dc.contributor.authorTunster, Simonen
dc.contributor.authorMcNally, Ben Den
dc.contributor.authorMurgia, Antonioen
dc.contributor.authorYusuf, Aishaen
dc.contributor.authorGriffin, Julian Len
dc.contributor.authorMurray, Andrewen
dc.contributor.authorWatson, Ericaen
dc.date.accessioned2020-03-18T00:30:35Z
dc.date.available2020-03-18T00:30:35Z
dc.date.issued2020-06en
dc.identifier.issn2214-4269
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/303568
dc.description.abstractNonalcoholic fatty liver disease (NAFLD) is associated with dietary folate deficiency and mutations in genes required for one-carbon 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 one-carbon 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.
dc.description.sponsorshipLister Institute for Preventative Medicine Centre for Trophoblast Research Evelyn Trust
dc.format.mediumElectronic-eCollectionen
dc.languageengen
dc.publisherElsevier
dc.rightsAll rights reserved
dc.rights.uri
dc.title<i>Mtrr</i> hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice.en
dc.typeArticle
prism.publicationDate2020en
prism.publicationNameMolecular genetics and metabolism reportsen
prism.startingPage100580
prism.volume23en
dc.identifier.doi10.17863/CAM.50645
dcterms.dateAccepted2020-03-15en
rioxxterms.versionofrecord10.1016/j.ymgmr.2020.100580en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-06en
dc.contributor.orcidSowton, Alice P [0000-0002-3718-7783]
dc.contributor.orcidTunster, Simon [0000-0002-2242-9452]
dc.contributor.orcidMurray, Andrew [0000-0002-0929-9315]
dc.contributor.orcidWatson, Erica [0000-0003-4496-2271]
dc.identifier.eissn2214-4269
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idLister Institute of Preventive Medicine ()
cam.orpheus.counter1*
rioxxterms.freetoread.startdate2023-03-17


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