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dc.contributor.authorvan Liempd, Sebastiaan
dc.contributor.authorCabrera, Diana
dc.contributor.authorPilzner, Carolin
dc.contributor.authorKollmus, Heike
dc.contributor.authorSchughart, Klaus
dc.contributor.authorFalcón-Pérez, Juan M
dc.date.accessioned2021-11-11T13:56:54Z
dc.date.available2021-11-11T13:56:54Z
dc.date.issued2021-10-09
dc.identifier.citationJ Biol Chem. 2021 Oct 9;297(5):101298. doi: 10.1016/j.jbc.2021.101298. Epub ahead of print.en_US
dc.identifier.pmid34637789
dc.identifier.doi10.1016/j.jbc.2021.101298
dc.identifier.urihttp://hdl.handle.net/10033/623093
dc.description.abstractInfluenza A virus (IAV) infection casts a significant burden on society. It has particularly high morbidity and mortality rates in patients suffering from metabolic disorders. The aim of this study was to relate metabolic changes with IAV susceptibility using well-characterized inbred mouse models. We compared the highly susceptible DBA/2J (D2) mouse strain for which IAV infection is lethal with the C57BL/6J (B6) strain, which exhibits a moderate course of disease and survives IAV infection. Previous studies showed that D2 has higher insulin and glucose levels and is predisposed to develop diet-induced type 2 diabetes. Using high-resolution liquid chromatography-coupled MS, the plasma metabolomes of individual animals were repeatedly measured up to 30 days postinfection. The biggest metabolic difference between these strains in healthy and infected states was in the levels of malonylcarnitine, which was consistently increased 5-fold in D2. Other interstrain and intrastrain differences in healthy and infected animals were observed for acylcarnitines, glucose, branched-chain amino acids, and oxidized fatty acids. By mapping metabolic changes to canonical pathways, we found that mitochondrial beta-oxidation is likely disturbed in D2 animals. In noninfected D2 mice, this leads to increased glycerolipid production and reduced acylcarnitine production, whereas in infected D2 animals, peroxisomal beta-oxidation becomes strongly increased. From these studies, we conclude that metabolic changes caused by a distortion of mitochondrial and peroxisomal metabolism might impact the innate immune response in D2, leading to high viral titers and mortality.en_US
dc.language.isoenen_US
dc.publisherElsevier/ASMBMen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectMSen_US
dc.subjectbeta-oxidationen_US
dc.subjectdiabetesen_US
dc.subjectinfluenza A virusen_US
dc.subjectmetabolomicsen_US
dc.subjectmouse modelen_US
dc.titleImpaired beta-oxidation increases vulnerability to influenza A infection.en_US
dc.typeArticleen_US
dc.identifier.eissn1083-351X
dc.identifier.journalThe Journal of biological chemistryen_US
dc.source.volume297
dc.source.issue5
dc.source.beginpage101298
dc.source.endpage
refterms.dateFOA2021-11-11T13:56:56Z
dc.source.journaltitleThe Journal of biological chemistry
dc.source.countryUnited States


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