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dc.contributor.authorRowland, Leslie A
dc.contributor.authorGuilherme, Adilson
dc.contributor.authorHenriques, Felipe
dc.contributor.authorDiMarzio, Chloe
dc.contributor.authorMunroe, Sean
dc.contributor.authorWetoska, Nicole
dc.contributor.authorKelly, Mark
dc.contributor.authorReddig, Keith
dc.contributor.authorHendricks, Gregory
dc.contributor.authorPan, Meixia
dc.contributor.authorHan, Xianlin
dc.contributor.authorIlkayeva, Olga R
dc.contributor.authorNewgard, Christopher B
dc.contributor.authorCzech, Michael P
dc.date.accessioned2023-05-02T18:13:46Z
dc.date.available2023-05-02T18:13:46Z
dc.date.issued2023-03-13
dc.identifier.citationRowland LA, Guilherme A, Henriques F, DiMarzio C, Munroe S, Wetoska N, Kelly M, Reddig K, Hendricks G, Pan M, Han X, Ilkayeva OR, Newgard CB, Czech MP. De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics. Nat Commun. 2023 Mar 13;14(1):1362. doi: 10.1038/s41467-023-37016-8. PMID: 36914626; PMCID: PMC10011520.en_US
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-023-37016-8en_US
dc.identifier.pmid36914626
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52017
dc.descriptionThis article is based on a previously available preprint in bioRxiv, https://doi.org/10.1101/2022.05.25.493413.en_US
dc.description.abstractAdipocytes robustly synthesize fatty acids (FA) from carbohydrate through the de novo lipogenesis (DNL) pathway, yet surprisingly DNL contributes little to their abundant triglyceride stored in lipid droplets. This conundrum raises the hypothesis that adipocyte DNL instead enables membrane expansions to occur in processes like autophagy, which requires an abundant supply of phospholipids. We report here that adipocyte Fasn deficiency in vitro and in vivo markedly impairs autophagy, evident by autophagosome accumulation and severely compromised degradation of the autophagic substrate p62. Our data indicate the impairment occurs at the level of autophagosome-lysosome fusion, and indeed, loss of Fasn decreases certain membrane phosphoinositides necessary for autophagosome and lysosome maturation and fusion. Autophagy dependence on FA produced by Fasn is not fully alleviated by exogenous FA in cultured adipocytes, and interestingly, imaging studies reveal that Fasn colocalizes with nascent autophagosomes. Together, our studies identify DNL as a critical source of FAs to fuel autophagosome and lysosome maturation and fusion in adipocytes.en_US
dc.language.isoenen_US
dc.relation.ispartofNature Communicationsen_US
dc.relation.urlhttps://doi.org/10.1038/s41467-023-37016-8en_US
dc.rights© The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.; Attribution 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectFat metabolismen_US
dc.subjectMacroautophagyen_US
dc.subjectMembrane lipidsen_US
dc.titleDe novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamicsen_US
dc.typeJournal Articleen_US
dc.source.journaltitleNature communications
dc.source.volume14
dc.source.issue1
dc.source.beginpage1362
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.identifier.journalNature communications
refterms.dateFOA2023-05-02T18:13:47Z
dc.contributor.departmentProgram in Molecular Medicineen_US
dc.contributor.departmentRadiologyen_US


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© The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.; Attribution 4.0 International
Except where otherwise noted, this item's license is described as © The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.; Attribution 4.0 International