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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.accessioned2020-12-21T03:18:49Z
dc.date.available2020-12-21T03:18:49Z
dc.date.issued2017-09-07
dc.identifierpii: 10.1038/s41467-017-00566-9
dc.identifier.citationItem, F., Wueest, S., Lemos, V., Stein, S., Lucchini, F. C., Denzler, R., Fisser, M. C., Challa, T. D., Pirinen, E., Kim, Y., Hemmi, S., Gulbins, E., Gross, A., O'Reilly, L. A., Stoffel, M., Auwerx, J. & Konrad, D. (2017). Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function. NATURE COMMUNICATIONS, 8 (1), https://doi.org/10.1038/s41467-017-00566-9.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/257151
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.Hepatic steatosis is a common disease closely associated with metabolic syndrome and insulin resistance. Here Item et al. show that Fas, a member of the TNF receptor superfamily, contributes to mitochondrial dysfunction, steatosis development, and insulin resistance under high fat diet.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleFas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function
dc.typeJournal Article
dc.identifier.doi10.1038/s41467-017-00566-9
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleNature Communications
melbourne.source.volume8
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1247453
melbourne.contributor.authorO'Reilly, Lorraine
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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