Targeting FoxO1 with AS1842856 Suppresses Adipogenesis

dc.contributor.authorZou, Pengen
dc.contributor.authorLiu, Longhuaen
dc.contributor.authorZheng, Louiseen
dc.contributor.authorLiu, Luen
dc.contributor.authorStoneman, Rebecca E.en
dc.contributor.authorCho, Aliciaen
dc.contributor.authorEmery, Ashleyen
dc.contributor.authorGilbert, Elizabeth R.en
dc.contributor.authorCheng, Zhiyongen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessioned2017-01-06T15:48:48Zen
dc.date.available2017-01-06T15:48:48Zen
dc.date.issued2014-12-01en
dc.description.abstractHyperplasia (i.e., increased adipogenesis) contributes to excess adiposity, the hallmark of obesity that can trigger metabolic complications. As FoxO1 has been implicated in adipogenic regulation, we investigated the kinetics of FoxO1 activation during adipocyte differentiation, and tested the effects of FoxO1 antagonist (AS1842856) on adipogenesis. We found for the first time that the kinetics of FoxO1 activation follows a series of sigmoid curves, and reveals the phases relevant to clonal expansion, cell cycle arrest, and the regulation of PPAR?, adiponectin, and mitochondrial proteins (complexes I and III). In addition, multiple activation-inactivation transitions exist in the stage of terminal differentiation. Importantly, persistent inhibition of FoxO1 with AS1842856 almost completely suppressed adipocyte differentiation, while selective inhibition in specific stages had differential effects on adipogenesis. Our data present a new view of FoxO1 in adipogenic regulation, and suggest AS1842856 can be an anti-obesity agent that warrants further investigation.en
dc.description.versionPublished versionen
dc.format.extent3759 - 3767 (9) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.4161/15384101.2014.965977en
dc.identifier.issn1538-4101en
dc.identifier.issue23en
dc.identifier.urihttp://hdl.handle.net/10919/73993en
dc.identifier.volume13en
dc.language.isoenen
dc.publisherTaylor & Francisen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000348329200018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution-NonCommercial 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en
dc.subjectCell Biologyen
dc.subjectadipogenesisen
dc.subjectAS1842856en
dc.subjectFoxO1en
dc.subjectmitochondriaen
dc.subjectObesityen
dc.subjectActivated receptor-gammaen
dc.subjectWhite adipose-tissueen
dc.subjectAdipocyte differentiationen
dc.subjectNutrient homeostasisen
dc.subjectInsulinen
dc.subjectFaten
dc.subjectCellsen
dc.titleTargeting FoxO1 with AS1842856 Suppresses Adipogenesisen
dc.title.serialCell Cycleen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Human Nutrition, Foods, & Exerciseen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
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