Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity

  1. Barradas, Marta 1
  2. Plaza, Adrian 1
  3. Colmenarejo, Gonzalo 2
  4. Lázaro, Iolanda 3
  5. Costa-Machado, Luis Filipe 4
  6. Martín-Hernández, Roberto 2
  7. Micó, Victor 5
  8. López-Aceituno, José Luis 4
  9. Herranz, Jesús 2
  10. Pantoja, Cristina 4
  11. Tejero, Hector 6
  12. Diaz-Ruiz, Alberto 7
  13. Al-Shahrour, Fatima 6
  14. Daimiel, Lidia 5
  15. Loria-Kohen, Viviana 8
  16. Ramirez de Molina, Ana 9
  17. Efeyan, Alejo 10
  18. Serrano, Manuel 11
  19. Pozo, Oscar J. 12
  20. Sala-Vila, Aleix 3
  21. Fernandez-Marcos, Pablo J. 4
  1. 1 1 Metabolic Syndrome Group – BIOPROMET. Madrid Institute for Advanced Studies - IMDEA Food, CEI UAM+CSIC, E28049, Madrid Spain.
  2. 2 Biostatistics and Bioinformatics Unit, CEI UAM+CSIC, Madrid Institute for Advanced Studies—IMDEA Food, Madrid, Spain
  3. 3 Cardiovascular risk and nutrition, Hospital del Mar Medical Research Institute—IMIM, Barcelona, Spain
  4. 4 Metabolic Syndrome Group—BIOPROMET, CEI UAM+CSIC, Madrid Institute for Advanced Studies—IMDEA Food, Madrid, Spain
  5. 5 Nutritional Genomics of Cardiovascular Disease and Obesity, Madrid Institute for Advanced Studies—IMDEA Food, Madrid, Spain
  6. 6 Bioinformatics Unit, Spanish National Cancer Research Centre—CNIO, Madrid, Spain
  7. 7 Nutritional Interventions Group, Precision Nutrition and Aging, CEI UAM+CSIC, Madrid Institute for Advanced Studies—IMDEA Food, Madrid, Spain
  8. 8 Nutrition and Clinical Trials Unit, Platform GENYAL, CEI UAM+CSIC, Madrid Institute for Advanced Studies—IMDEA Food, Madrid, Spain
  9. 9 Nutrition and Clinical Trials Unit, Platform GENYAL, CEI UAM+CSIC, Madrid Institute for Advanced Studies—IMDEA Food, Madrid, Spain Molecular Oncology and Nutritional Genomics of Cancer Group, CEI UAM+CSIC, Madrid Institute for Advanced Studies—IMDEA Food, Madrid, Spain
  10. 10 Metabolism and Cell Signaling Group, Spanish National Cancer Research Centre—CNIO, Madrid, Spain
  11. 11 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
  12. 12 Applied Metabolomics Research Group, Hospital del Mar Medical Research Institute—(IMIM), Barcelona, Spain
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Éditeur: Zenodo

Année de publication: 2022

Type: Dataset

CC BY 4.0

DOI: 10.5281/ZENODO.6958418 lock_openAccès ouvert editor

Résumé

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.