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dc.contributor.authorKarlsen, Tom Rune
dc.contributor.authorKong, Xiang Yi
dc.contributor.authorHolm, Sverre
dc.contributor.authorQuiles-Jiménez, Ana M T
dc.contributor.authorDahl, Tuva Børresdatter
dc.contributor.authorYang, Kuan
dc.contributor.authorSagen, Ellen Lund
dc.contributor.authorSkarpengland, Tonje
dc.contributor.authorØgaard, Jonas
dc.contributor.authorHolm, Kristian
dc.contributor.authorVestad, Beate
dc.contributor.authorOlsen, Maria Belland
dc.contributor.authorAukrust, Pål
dc.contributor.authorBjørås, Magnar
dc.contributor.authorHov, Johannes Espolin Roksund
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorGregersen, Ida
dc.identifier.citationScientific Reports. 2021, 11 (1), .en_US
dc.description.abstractAtherosclerosis and its consequences cause considerable morbidity and mortality world-wide. We have previously shown that expression of the DNA glycosylase NEIL3 is regulated in human atherosclerotic plaques, and that NEIL3-deficiency enhances atherogenesis in Apoe−/− mice. Herein, we identified a time point prior to quantifiable differences in atherosclerosis between Apoe−/−Neil3−/− mice and Apoe−/− mice. Mice at this age were selected to explore the metabolic and pathophysiological processes preceding extensive atherogenesis in NEIL3-deficient mice. Untargeted metabolomic analysis of young Apoe−/−Neil3−/− mice revealed significant metabolic disturbances as compared to mice expressing NEIL3, particularly in metabolites dependent on the gut microbiota. 16S rRNA gene sequencing of fecal bacterial DNA indeed confirmed that the NEIL3-deficient mice had altered gut microbiota, as well as increased circulating levels of the bacterially derived molecule LPS. The mice were challenged with a FITC-conjugated dextran to explore gut permeability, which was significantly increased in the NEIL3-deficient mice. Further, immunohistochemistry showed increased levels of the proliferation marker Ki67 in the colonic epithelium of NEIL3-deficient mice, suggesting increased proliferation of intestinal cells and gut leakage. We suggest that these metabolic alterations serve as drivers of atherosclerosis in NEIL3-deficient mice.en_US
dc.publisherNature Researchen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleNEIL3-deficiency increases gut permeability and contributes to a pro-atherogenic metabolic phenotypeen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.source.journalScientific Reportsen_US

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