Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity

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  • dc.contributor.author Barradas, Marta
  • dc.contributor.author Lázaro, Iolanda
  • dc.contributor.author Pozo Mendoza, Óscar J., 1975-
  • dc.contributor.author Sala Vila, Aleix
  • dc.contributor.author Fernandez-Marcos, Pablo J.
  • dc.date.accessioned 2023-02-09T08:07:16Z
  • dc.date.available 2023-02-09T08:07:16Z
  • dc.date.issued 2022
  • dc.description.abstract Fasting exerts beneficial effects in mice and humans, including protection from chemotherapy toxicity. To explore the involved mechanisms, we collect blood from humans and mice before and after 36 or 24 hours of fasting, respectively, and measure lipid composition of erythrocyte membranes, circulating micro RNAs (miRNAs), and RNA expression at peripheral blood mononuclear cells (PBMCs). Fasting coordinately affects the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane; and reduces the expression of insulin signaling-related genes in PBMCs. When fasted for 24 hours before and 24 hours after administration of oxaliplatin or doxorubicin, mice show a strong protection from toxicity in several tissues. Erythrocyte membrane lipids and PBMC gene expression define two separate groups of individuals that accurately predict a differential protection from chemotherapy toxicity, with important clinical implications. Our results reveal a mechanism of fasting associated with lipid homeostasis, and provide biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity.
  • dc.description.sponsorship Work at the laboratory of P.J.F.M. is funded by the Ramón Areces Foundation, (CIVP18A3891), Asociación Española contra el Cáncer-AECC (SIRTBIO—LABAE18008FERN), a Ramon y Cajal Award from the Spanish Ministry of Science, Innovation and Universities (MICINN) (RYC-2017-22335), RETOS projects Program of MICINN (SAF2017-85766-R) and the Portuguese Foundation for Science and Technology (FCT-MCTES, SFRH/BD/124022/2016). Work at the laboratory of ARM was funded by the MICINN (PID2019-110183RB-C21), Regional Government of Community of Madrid (P2018/BAA-4343-ALIBIRD2020-CM) and the Ramón Areces Foundation. Work at the laboratory of A.D.R. Funded by the Comunidad de Madrid—Talento Grant 2018-T1/BMD-11966 and the MICINN PID-2019-106893RA-100. Work at the laboratory of L.D. is funded by projects from the Health Research Fund (ISCIII FIS PI14/01374 and FISPI17/00508) and from a Manuel de Oya research fellowship from the Beer and Health Foundation. Work at the laboratory of A.E. is funded by a Ramon y Cajal Award from MICINN (RYC-2013-13546) and RETOS projects Program of the MICINN, co-funded by the European Regional Development Fund (ERDF) (SAF2015-67538-R). Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and the “laCaixa” Foundation.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Barradas M, Plaza A, Colmenarejo G, Lázaro I, Costa-Machado LF, Martín-Hernández R, et al. Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity. Nat Commun. 2022 Sep 27;13(1):5677. DOI: 10.1038/s41467-022-33352-3
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-022-33352-3
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/55682
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Commun. 2022 Sep 27;13(1):5677
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/669622
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-85766-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110183RB-C21
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-67538-R
  • dc.rights © The Author(s) 2022. 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/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Chemotherapy
  • dc.subject.keyword Fat metabolism
  • dc.title Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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