Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood

作者：Takayuki Teruya, Romanas Chaleckis, Junko Takada, Mitsuhiro Yanagida, Hiroshi Kondoh · 发表于：Scientific Reports · 年份：2019 · DOI：10.1038/s41598-018-36674-9 · 被引用次数：87 · 研究领域：Metabolomics and Mass Spectrometry Studies、Diet and metabolism studies、Cancer, Hypoxia, and Metabolism

During human fasting, metabolic markers, including butyrates, carnitines, and branched-chain amino acids, are upregulated for energy substitution through gluconeogenesis and use of stored lipids. We performed non-targeted, accurate semiquantitative metabolomic analysis of human whole blood, plasma, and red blood cells during 34-58 hr fasting of four volunteers. During this period, 44 of ~130 metabolites increased 1.5~60-fold. Consistently fourteen were previously reported. However, we identified another 30 elevated metabolites, implicating hitherto unrecognized metabolic mechanisms induced by fasting. Metabolites in pentose phosphate pathway are abundant, probably due to demand for antioxidants, NADPH, gluconeogenesis and anabolic metabolism. Global increases of TCA cycle-related compounds reflect enhanced mitochondrial activity in tissues during fasting. Enhanced purine/pyrimidine metabolites support RNA/protein synthesis and transcriptional reprogramming, which is promoted also by some fasting-related metabolites, possibly via epigenetic modulations. Thus diverse, pronounced metabolite increases result from greatly activated catabolism and anabolism stimulated by fasting. Anti-oxidation may be a principal response to fasting.