An Organism-Level Quantitative Flux Model of Mammalian Energy Metabolism.
An Organism-Level Quantitative Flux Model of Mammalian Energy Metabolism.
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哺乳动物能量代谢的生物体水平定量通量模型。
DOI：
10.1101/2024.02.11.579776
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Hui,Sheng
中科院分区：
文献类型：
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作者：
Yuan,Bo;Inouye,KarenE;Hotamışlıgil,GökhanS;Hui,Sheng
哺乳动物的组织以血液循环中的营养物质为食。在生物体水平上，哺乳动物的能量代谢包括循环营养物质的氧化、储存、相互转换和释放。在这里，通过整合同位素示踪剂输注，质谱和同位素气体分析仪测量，我们开发了一个框架，系统地量化通过这些代谢过程中的10个主要循环能量营养素在小鼠中的通量，从而在生物体水平的定量通量模型的能量代谢。该模型显示，在野生型小鼠循环营养素的代谢循环通量占主导地位的氧化通量，循环和氧化之间的个别循环营养素的不同分区。在肥胖小鼠模型中的应用表明，在ob/ob小鼠中代谢循环通量的广泛升高，但在饮食诱导的肥胖小鼠中，每只动物或每瘦体重的基础上没有。我们的框架是一个有价值的工具，以揭示在生理和疾病条件下的能量代谢的新功能。
Mammalian tissues feed on nutrients in the blood circulation. At the organism level, mammalian energy metabolism is comprised of the oxidation, storage, interconversion, and release of circulating nutrients. Here, by integrating isotope tracer infusion, mass spectrometry, and isotope gas analyzer measurement, we developed a framework to systematically quantify fluxes through these metabolic processes for 10 major circulating energy nutrients in mice, resulting in an organism-level quantitative flux model of energy metabolism. This model revealed in wild-type mice that circulating nutrients have metabolic cycling fluxes dominant to their oxidation fluxes, with distinct partitions between cycling and oxidation for individual circulating nutrients. Applications of this framework in obese mouse models showed extensive elevation of metabolic cycling fluxes in ob/ob mice but not in diet-induced obese mice on a per-animal or per-lean mass basis. Our framework is a valuable tool to reveal new features of energy metabolism in physiological and disease conditions.