Show simple item record

dc.contributor.authorItem F
dc.contributor.authorWueest S
dc.contributor.authorLemos V
dc.contributor.authorStein S
dc.contributor.authorLucchini FC
dc.contributor.authorDenzler R
dc.contributor.authorFisser MC
dc.contributor.authorChalla TD
dc.contributor.authorPirinen E
dc.contributor.authorKim Y
dc.contributor.authorHemmi S
dc.contributor.authorGulbins E
dc.contributor.authorGross A
dc.contributor.authorO'Reilly LA
dc.contributor.authorStoffel M
dc.contributor.authorAuwerx J
dc.contributor.authorKonrad D
dc.date.accessioned2018-01-16T11:41:01Z
dc.date.available2018-01-16T11:41:01Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/5190
dc.description.abstractNonalcoholic fatty liver disease is one of the most prevalent metabolic disorders and it tightly associates with obesity, type 2 diabetes, and cardiovascular disease. Reduced mitochondrial lipid oxidation contributes to hepatic fatty acid accumulation. Here, we show that the Fas cell surface death receptor (Fas/CD95/Apo-1) regulates hepatic mitochondrial metabolism. Hepatic Fas overexpression in chow-fed mice compromises fatty acid oxidation, mitochondrial respiration, and the abundance of mitochondrial respiratory complexes promoting hepatic lipid accumulation and insulin resistance. In line, hepatocyte-specific ablation of Fas improves mitochondrial function and ameliorates high-fat-diet-induced hepatic steatosis, glucose tolerance, and insulin resistance. Mechanistically, Fas impairs fatty acid oxidation via the BH3 interacting-domain death agonist (BID). Mice with genetic or pharmacological inhibition of BID are protected from Fas-mediated impairment of mitochondrial oxidation and hepatic steatosis. We suggest Fas as a potential novel therapeutic target to treat obesity-associated fatty liver and insulin resistance.en
dc.language.isoENen
dc.publisherSpringer Natureen
dc.relation.ispartofseriesNature Communicationsen
dc.relation.urihttp://dx.doi.org/10.1038/s41467-017-00566-9en
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/en
dc.subjectMetabolic syndromeen
dc.subjectNon-alcoholic fatty liver diseaseen
dc.subjectType 2 diabetesen
dc.titleFas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial functionen
dc.description.versionpublished versionen
dc.contributor.departmentA.I. Virtanen -instituuttien
uef.solecris.id49447645en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.doi10.1038/s41467-017-00566-9en
dc.description.reviewstatuspeerRevieweden
dc.relation.articlenumber480en
dc.relation.issn2041-1723en
dc.relation.volume8en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
uef.solecris.openaccessOpen access -julkaisukanavassa ilmestynyt julkaisu


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record