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dc.date.accessioned2020-03-19T20:23:33Z
dc.date.available2020-03-19T20:23:33Z
dc.date.created2019-08-05T10:31:33Z
dc.date.issued2019
dc.identifier.citationPettersen, Ina Katrine Nitschke Tusubira, Deusdedit Ashrafi, Hanan Dyrstad, Sissel Elisabeth Hansen, Lena Liu, Xiao-Zheng Hodneland, Linn I. Løvsletten, Nils Gunnar Berge, Kjetil Wergedahl, Hege Bjørndal, Bodil Fluge, Øystein Bruland, Ove Rustan, Arild Halberg, Nils Røsland, Gro Vatne Berge, Rolf Kristian Tronstad, Karl Johan . Upregulated PDK4 expression is a sensitive marker of increased fatty acid oxidation. Mitochondrion (Amsterdam. Print). 2019, 49, 97-110
dc.identifier.urihttp://hdl.handle.net/10852/74093
dc.description.abstractFatty acid oxidation is a central fueling pathway for mitochondrial ATP production. Regulation occurs through multiple nutrient- and energy-sensitive molecular mechanisms. We explored if upregulated mRNA expression of the mitochondrial enzyme pyruvate dehydrogenase kinase 4 (PDK4) may be used as a surrogate marker of increased mitochondrial fatty acid oxidation, by indicating an overall shift from glucose to fatty acids as the preferred oxidation fuel. The association between fatty acid oxidation and PDK4 expression was studied in different contexts of metabolic adaption. In rats treated with the modified fatty acid tetradecylthioacetic acid (TTA), Pdk4 was upregulated simultaneously with fatty acid oxidation genes in liver and heart, whereas muscle and white adipose tissue remained unaffected. In MDA-MB-231 cells, fatty acid oxidation increased nearly three-fold upon peroxisome proliferator-activated receptor α (PPARα, PPARA) overexpression, and four-fold upon TTA-treatment. PDK4 expression was highly increased under these conditions. Further, overexpression of PDK4 caused increased fatty acid oxidation in these cells. Pharmacological activators of PPARα and AMPK had minor effects, while the mTOR inhibitor rapamycin potentiated the effect of TTA. There were minor changes in mitochondrial respiration, glycolytic function, and mitochondrial biogenesis under conditions of increased fatty acid oxidation. TTA was found to act as a mild uncoupler, which is likely to contribute to the metabolic effects. Repeated experiments with HeLa cells supported these findings. In summary, PDK4 upregulation implies an overarching metabolic shift towards increased utilization of fatty acids as energy fuel, and thus constitutes a sensitive marker of enhanced fatty acid oxidation.en_US
dc.languageEN
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleUpregulated PDK4 expression is a sensitive marker of increased fatty acid oxidationen_US
dc.typeJournal articleen_US
dc.creator.authorPettersen, Ina Katrine Nitschke
dc.creator.authorTusubira, Deusdedit
dc.creator.authorAshrafi, Hanan
dc.creator.authorDyrstad, Sissel Elisabeth
dc.creator.authorHansen, Lena
dc.creator.authorLiu, Xiao-Zheng
dc.creator.authorHodneland, Linn I.
dc.creator.authorLøvsletten, Nils Gunnar
dc.creator.authorBerge, Kjetil
dc.creator.authorWergedahl, Hege
dc.creator.authorBjørndal, Bodil
dc.creator.authorFluge, Øystein
dc.creator.authorBruland, Ove
dc.creator.authorRustan, Arild
dc.creator.authorHalberg, Nils
dc.creator.authorRøsland, Gro Vatne
dc.creator.authorBerge, Rolf Kristian
dc.creator.authorTronstad, Karl Johan
cristin.unitcode185,15,23,30
cristin.unitnameSeksjon for farmakologi og farmasøytisk biovitenskap
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1713984
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Mitochondrion (Amsterdam. Print)&rft.volume=49&rft.spage=97&rft.date=2019
dc.identifier.jtitleMitochondrion (Amsterdam. Print)
dc.identifier.volume49
dc.identifier.startpage97
dc.identifier.endpage110
dc.identifier.doihttps://doi.org/10.1016/j.mito.2019.07.009
dc.identifier.urnURN:NBN:no-77195
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn1567-7249
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/74093/1/pettersen.pdf
dc.type.versionPublishedVersion
dc.relation.projectNFR/272680


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