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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.
Fasting has been reported to protect from chemotherapy-associated toxicity. Here, the authors show that fatty acid profiles in erythrocyte membranes and gene expression from peripheral blood mononuclear cells are associated to the fasting-mediated benefits during cancer treatment in mice and patients.
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1 Madrid Institute for Advanced Studies—IMDEA Food, Metabolic Syndrome Group—BIOPROMET, CEI UAM+CSIC, Madrid, Spain (GRID:grid.429045.e) (ISNI:0000 0004 0500 5230)
2 Madrid Institute for Advanced Studies—IMDEA Food, Biostatistics and Bioinformatics Unit, CEI UAM+CSIC, Madrid, Spain (GRID:grid.429045.e) (ISNI:0000 0004 0500 5230)
3 Hospital del Mar Medical Research Institute—IMIM, Cardiovascular risk and nutrition, Barcelona, Spain (GRID:grid.411142.3) (ISNI:0000 0004 1767 8811)
4 Madrid Institute for Advanced Studies—IMDEA Food, Nutritional Genomics of Cardiovascular Disease and Obesity, Madrid, Spain (GRID:grid.429045.e) (ISNI:0000 0004 0500 5230)
5 Spanish National Cancer Research Centre—CNIO, Bioinformatics Unit, Madrid, Spain (GRID:grid.7719.8) (ISNI:0000 0000 8700 1153)
6 Madrid Institute for Advanced Studies—IMDEA Food, Nutritional Interventions Group, Precision Nutrition and Aging, CEI UAM+CSIC, Madrid, Spain (GRID:grid.429045.e) (ISNI:0000 0004 0500 5230)
7 Madrid Institute for Advanced Studies—IMDEA Food, Nutrition and Clinical Trials Unit, Platform GENYAL, CEI UAM+CSIC, Madrid, Spain (GRID:grid.429045.e) (ISNI:0000 0004 0500 5230)
8 Madrid Institute for Advanced Studies—IMDEA Food, Nutrition and Clinical Trials Unit, Platform GENYAL, CEI UAM+CSIC, Madrid, Spain (GRID:grid.429045.e) (ISNI:0000 0004 0500 5230); Madrid Institute for Advanced Studies—IMDEA Food, Molecular Oncology and Nutritional Genomics of Cancer Group, CEI UAM+CSIC, Madrid, Spain (GRID:grid.429045.e) (ISNI:0000 0004 0500 5230)
9 Spanish National Cancer Research Centre—CNIO, Metabolism and Cell Signaling Group, Madrid, Spain (GRID:grid.7719.8) (ISNI:0000 0000 8700 1153)
10 Catalan Institution for Research and Advanced Studies (ICREA), Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain (GRID:grid.425902.8) (ISNI:0000 0000 9601 989X)
11 Hospital del Mar Medical Research Institute—(IMIM), Applied Metabolomics Research Group, Barcelona, Spain (GRID:grid.411142.3) (ISNI:0000 0004 1767 8811)
12 Hospital del Mar Medical Research Institute—IMIM, Cardiovascular risk and nutrition, Barcelona, Spain (GRID:grid.411142.3) (ISNI:0000 0004 1767 8811); Fatty Acid Research Institute, Sioux Falls, USA (GRID:grid.411142.3)