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Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity

Author

Listed:
  • 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
    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
    Fatty Acid Research Institute)

  • Pablo J. Fernandez-Marcos

    (Madrid Institute for Advanced Studies—IMDEA Food)

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.

Suggested Citation

  • 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 , 2022. "Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33352-3
    DOI: 10.1038/s41467-022-33352-3
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    References listed on IDEAS

    as
    1. Stefanie Groot & Rieneke T. Lugtenberg & Danielle Cohen & Marij J. P. Welters & Ilina Ehsan & Maaike P. G. Vreeswijk & Vincent T. H. B. M. Smit & Hiltje Graaf & Joan B. Heijns & Johanneke E. A. Portie, 2020. "Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    2. Evanna L. Mills & Kerry A. Pierce & Mark P. Jedrychowski & Ryan Garrity & Sally Winther & Sara Vidoni & Takeshi Yoneshiro & Jessica B. Spinelli & Gina Z. Lu & Lawrence Kazak & Alexander S. Banks & Mar, 2018. "Accumulation of succinate controls activation of adipose tissue thermogenesis," Nature, Nature, vol. 560(7716), pages 102-106, August.
    Full references (including those not matched with items on IDEAS)

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