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小鼠口服 13C-葡萄糖耐量试验的代谢组学图谱

Metabolomics atlas of oral 13C-glucose tolerance test in mice.

机构信息

Laboratory of Metabolism of Bioactive Lipids, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic.

Laboratory of Translational Metabolism, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic.

出版信息

Cell Rep. 2021 Oct 12;37(2):109833. doi: 10.1016/j.celrep.2021.109833.

DOI:10.1016/j.celrep.2021.109833
PMID:34644567
Abstract

Glucose tolerance represents a complex phenotype in which many tissues play important roles and interact to regulate metabolic homeostasis. Here, we perform an analysis of C-glucose tissue distribution, which maps the metabolome and lipidome across 12 metabolically relevant mouse organs and plasma, with integrated C-glucose-derived carbon tracing during oral glucose tolerance test (OGTT). We measure time profiles of water-soluble metabolites and lipids and integrate the global metabolite response into metabolic pathways. During the OGTT, glucose use is turned on with specific kinetics at the organ level, but fasting substrates like β-hydroxybutyrate are switched off in all organs simultaneously. Timeline profiling of C-labeled fatty acids and triacylglycerols across tissues suggests that brown adipose tissue may contribute to the circulating fatty acid pool at maximal plasma glucose levels. The GTTAtlas interactive web application serves as a unique resource for the exploration of whole-body glucose metabolism and time profiles of tissue and plasma metabolites during the OGTT.

摘要

葡萄糖耐量是一种复杂的表型,其中许多组织发挥着重要作用,并相互作用以调节代谢稳态。在这里,我们对 C-葡萄糖组织分布进行了分析,该分析绘制了 12 种与代谢相关的小鼠器官和血浆中的代谢组和脂质组图谱,并在口服葡萄糖耐量试验 (OGTT) 期间整合了 C-葡萄糖衍生的碳示踪。我们测量了水溶性代谢物和脂质的时间曲线,并将全局代谢物反应整合到代谢途径中。在 OGTT 期间,葡萄糖的利用在器官水平上以特定的动力学开启,但像β-羟基丁酸这样的空腹底物在所有器官中同时关闭。跨组织的 C 标记脂肪酸和三酰甘油的时间线分析表明,棕色脂肪组织可能有助于在最大血糖水平下循环脂肪酸池。GTTAtlas 交互式网络应用程序是探索全身葡萄糖代谢以及 OGTT 期间组织和血浆代谢物时间曲线的独特资源。

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