Metabolic Syndrome Group-BIOPROMET, CEI UAM+CSIC, Madrid Institute for Advanced Studies-IMDEA Food, Madrid, Spain.
Biostatistics and Bioinformatics Unit, CEI UAM+CSIC, Madrid Institute for Advanced Studies-IMDEA Food, Madrid, Spain.
Nat Commun. 2022 Sep 27;13(1):5677. doi: 10.1038/s41467-022-33352-3.
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.
禁食对小鼠和人类都有有益的影响，包括预防化疗毒性。为了探索相关机制，我们分别在人类和小鼠禁食 36 小时或 24 小时前后采集血液，测量红细胞膜的脂质组成、循环 microRNAs (miRNAs) 和外周血单个核细胞 (PBMC) 的 RNA 表达。禁食协调地影响红细胞膜上多不饱和与饱和和单不饱和脂肪酸的比例；并降低 PBMC 中胰岛素信号相关基因的表达。在奥沙利铂或阿霉素给药前禁食 24 小时，然后再禁食 24 小时，小鼠在多个组织中表现出对毒性的强烈保护。红细胞膜脂质和 PBMC 基因表达定义了两个独立的个体组，可准确预测化疗毒性的差异保护，具有重要的临床意义。我们的结果揭示了与脂质平衡相关的禁食机制，并提供了预测禁食介导的化疗毒性保护的禁食生物标志物。
