Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity

Marta Barradas (), Adrián Plaza (), Gonzalo Colmenarejo, Iolanda Lázaro, Luis Filipe Costa-Machado, Roberto Martín-Hernández, Victor Micó, José Luis López-Aceituno, Jesús Herranz, Cristina Pantoja, Hector Tejero, Alberto Diaz-Ruiz, Fatima Al-Shahrour, Lidia Daimiel, Viviana Loria-Kohen, Ana Ramirez de Molina, Alejo Efeyan, Manuel Serrano, Oscar J. Pozo, Aleix Sala-Vila and Pablo J. Fernandez-Marcos ()
Additional contact information
Marta Barradas: Madrid Institute for Advanced Studies—IMDEA Food
Adrián Plaza: Madrid Institute for Advanced Studies—IMDEA Food
Gonzalo Colmenarejo: Madrid Institute for Advanced Studies—IMDEA Food
Iolanda Lázaro: Hospital del Mar Medical Research Institute—IMIM
Luis Filipe Costa-Machado: Madrid Institute for Advanced Studies—IMDEA Food
Roberto Martín-Hernández: Madrid Institute for Advanced Studies—IMDEA Food
Victor Micó: Madrid Institute for Advanced Studies—IMDEA Food
José Luis López-Aceituno: Madrid Institute for Advanced Studies—IMDEA Food
Jesús Herranz: Madrid Institute for Advanced Studies—IMDEA Food
Cristina Pantoja: Madrid Institute for Advanced Studies—IMDEA Food
Hector Tejero: Spanish National Cancer Research Centre—CNIO
Alberto Diaz-Ruiz: Madrid Institute for Advanced Studies—IMDEA Food
Fatima Al-Shahrour: Spanish National Cancer Research Centre—CNIO
Lidia Daimiel: Madrid Institute for Advanced Studies—IMDEA Food
Viviana Loria-Kohen: Madrid Institute for Advanced Studies—IMDEA Food
Ana Ramirez de Molina: Madrid Institute for Advanced Studies—IMDEA Food
Alejo Efeyan: Spanish National Cancer Research Centre—CNIO
Manuel Serrano: Catalan Institution for Research and Advanced Studies (ICREA)
Oscar J. Pozo: Hospital del Mar Medical Research Institute—(IMIM)
Aleix Sala-Vila: Hospital del Mar Medical Research Institute—IMIM
Pablo J. Fernandez-Marcos: Madrid Institute for Advanced Studies—IMDEA Food

Nature Communications, 2022, vol. 13, issue 1, 1-22

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33352-3

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DOI: 10.1038/s41467-022-33352-3

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