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dc.contributor.authorToivonen, Raine
dc.contributor.authorVanhatalo, Sanja
dc.contributor.authorHollmén, Maija
dc.contributor.authorMunukka, Eveliina
dc.contributor.authorKeskitalo, Anniina
dc.contributor.authorPietilä, Sami
dc.contributor.authorElo, Laura
dc.contributor.authorHuovinen, Pentti
dc.contributor.authorJalkanen, Sirpa
dc.contributor.authorPekkala, Satu
dc.date.accessioned2021-02-22T09:45:05Z
dc.date.available2021-02-22T09:45:05Z
dc.date.issued2021
dc.identifier.citationToivonen, Raine; Vanhatalo, Sanja; Hollmén, Maija; Munukka, Eveliina; Keskitalo, Anniina; Pietilä, Sami; Elo, Laura; Huovinen, Pentti; Jalkanen, Sirpa; Pekkala, Satu (2021). Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis. Sci, 3 (1), 13. DOI: 10.3390/sci3010013
dc.identifier.otherCONVID_34464443
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/74330
dc.description.abstractToll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.en
dc.format.mimetypeapplication/pdf
dc.languageeng
dc.publisherMDPI
dc.relation.ispartofseriesSci
dc.rightsCC BY 4.0
dc.subject.othergut microbiota
dc.subject.otherliver
dc.subject.othermetabolism
dc.subject.otherinflammation
dc.titleVascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202102221724
dc.contributor.laitosLiikuntatieteellinen tiedekuntafi
dc.contributor.laitosFaculty of Sport and Health Sciencesen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.description.reviewstatuspeerReviewed
dc.relation.issn2413-4155
dc.relation.numberinseries1
dc.relation.volume3
dc.type.versionpublishedVersion
dc.rights.copyright© 2021 the Authors
dc.rights.accesslevelopenAccessfi
dc.relation.grantnumber267719
dc.subject.ysosuolistomikrobisto
dc.subject.ysotulehdus
dc.subject.ysomaksa
dc.subject.ysoaineenvaihdunta
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p37925
jyx.subject.urihttp://www.yso.fi/onto/yso/p1049
jyx.subject.urihttp://www.yso.fi/onto/yso/p11264
jyx.subject.urihttp://www.yso.fi/onto/yso/p3066
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.3390/sci3010013
dc.relation.funderSuomen Akatemiafi
dc.relation.funderAcademy of Finlanden
jyx.fundingprogramTutkijatohtori, SAfi
jyx.fundingprogramPostdoctoral Researcher, AoFen
jyx.fundinginformationThis study was financially supported by the Academy of Finland postdoctoral research fellowships for Raine Toivonen (285503) and Satu Pekkala (267719), by the Academy of Finland Researcher fellowship for Satu Pekkala (308042) and by the Academy Professorship for Sirpa Jalkanen (272239). In addition, funding was granted to Satu Pekkala by the Finnish Diabetes Research Foundation, by the Finnish Culture Foundation and by the Finnish Instrumentarium Research Foundation.


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