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dc.contributor.authorHall, Zoeen
dc.contributor.authorBond, Nicholas Jen
dc.contributor.authorAshmore, Tomen
dc.contributor.authorSanders, Francisen
dc.contributor.authorAment, Zsuzsannaen
dc.contributor.authorWang, Xinzhuen
dc.contributor.authorMurray, Andrewen
dc.contributor.authorBellafante, Elenaen
dc.contributor.authorVirtue, Samuelen
dc.contributor.authorVidal-Puig, Antonioen
dc.contributor.authorAllison, Michaelen
dc.contributor.authorDavies, Susan Een
dc.contributor.authorKoulman, Alberten
dc.contributor.authorVacca, Micheleen
dc.contributor.authorGriffin, Julianen
dc.date.accessioned2017-02-08T16:29:49Z
dc.date.available2017-02-08T16:29:49Z
dc.date.issued2017-04en
dc.identifier.issn0270-9139
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/262382
dc.description.abstractNon-alcoholic fatty liver disease (NAFLD) can progress from 'simple steatosis' (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis and cancer. Currently the driver for this progression is not fully understood; in particular it is not known how NAFLD and its early progression affects the distribution of lipids in the liver, producing lipotoxicity and inflammation. Here we use dietary and genetic mouse models of NAFL and NASH, and translate results to humans, by correlating the spatial distribution of lipids in liver tissue with disease progression, using advanced mass spectrometry imaging technology. We identified several lipids with distinct zonal distributions in control and NAFL samples, whilst partial to complete loss of lipid zonation was found in NASH. In addition, we found increased hepatic expression of genes associated with remodelling the phospholipid membrane, release of arachidonic acid (AA) from the membrane, and production of eicosanoid species which promote inflammation and cell injury. Using immunohistochemistry, we further suggest that the zonal location of remodelling enzyme lysophosphatidylcholine acyl transferase 2 (LPCAT2) plays a role in the change in spatial distribution for arachidonic acid (AA)-containing lipids. This results in a cycle of AA-enrichment in pericentral hepatocytes, membrane release of AA and generation of pro-inflammatory eicosanoids, and may account for increased oxidative damage in pericentral regions in NASH. CONCLUSION: We have demonstrated that NAFLD is associated not only with lipid enrichment, but also to zonal changes of specific lipids and their associated metabolic pathways. This may play a role in the heterogeneous development of NAFLD.
dc.description.sponsorshipMedical Research Council (MRC). Horizon 2020 Framework Program of the European Union.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.language.isoenen
dc.publisherWiley
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectLiver Neoplasmsen
dc.subjectFatty Liveren
dc.subjectLiver Cirrhosisen
dc.subjectDisease Models, Animalen
dc.subjectEicosanoidsen
dc.subjectPhospholipidsen
dc.subjectBiopsy, Needleen
dc.subjectPrognosisen
dc.subjectSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionizationen
dc.subjectImmunohistochemistryen
dc.subjectSeverity of Illness Indexen
dc.subjectRisk Assessmenten
dc.subjectRandom Allocationen
dc.subjectLiver Regenerationen
dc.subjectMaleen
dc.subjectMass Spectrometryen
dc.subjectDiet, High-Faten
dc.subjectNon-alcoholic Fatty Liver Diseaseen
dc.subjectDiet, Westernen
dc.titleLipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease.en
dc.typeArticle
prism.endingPage1180
prism.publicationDate2017en
prism.publicationNameHepatology (Baltimore, Md.)en
prism.startingPage1165
prism.volume65en
dc.identifier.doi10.17863/CAM.7646
dcterms.dateAccepted2016-11-11en
rioxxterms.versionofrecord10.1002/hep.28953en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-04en
dc.contributor.orcidHall, Zoe [0000-0002-1434-8329]
dc.contributor.orcidMurray, Andrew [0000-0002-0929-9315]
dc.contributor.orcidVidal-Puig, Antonio [0000-0003-4220-9577]
dc.contributor.orcidKoulman, Albert [0000-0001-9998-051X]
dc.contributor.orcidVacca, Michele [0000-0002-1973-224X]
dc.contributor.orcidGriffin, Julian [0000-0003-1336-7744]
dc.identifier.eissn1527-3350
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/P011705/1)
pubs.funder-project-idMRC (G0400192)
pubs.funder-project-idMRC (MC_G0802535)
pubs.funder-project-idBBSRC (BB/H002731/1)
pubs.funder-project-idMRC (G0600717B)
pubs.funder-project-idMRC (G0802051)
pubs.funder-project-idMRC (MC_UU_12012/2)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (634413)
pubs.funder-project-idMedical Research Council (MC_PC_13030)
cam.orpheus.successThu Jan 30 12:57:07 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International