Metabolic flux between organs measured by arteriovenous metabolite gradients.
Metabolic flux between organs measured by arteriovenous metabolite gradients.
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DOI：
10.1038/s12276-022-00803-2
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发表时间：
2022-09
影响因子：
12.8
通讯作者：
Jang, Cholsoon
中科院分区：
文献类型：
--
作者：
Bae, Hosung;Lam, Katie;Jang, Cholsoon
哺乳动物的器官将饮食中的营养物质转化为循环代谢产物，并分享它们，以维持全身代谢的动态平衡。虽然循环代谢物的浓度经常在各种病理生理条件下被测量，但由于技术上的困难，循环代谢物在器官之间的交换流量不易测量。同位素示踪对于测量感兴趣的代谢物的这种通量是有用的，但代谢物之间的同位素原子的洗牌需要数学建模。动静脉代谢物梯度测量可以补充同位素示踪，以同时推断许多代谢物特定器官的净通量。在这里，我们回顾了动静脉测量的历史发展，并讨论了它们的优势和局限性，关键的例子研究揭示了不同病理生理背景下器官之间的代谢物交换流量。测量血液中进入和离开器官的代谢物，如脂质或脂肪酸的浓度，可以揭示该器官是否使用或产生该代谢物。器官将食物转化为代谢物，并专门产生不同的代谢物。然后这些代谢物在器官之间共享；浓度受到严格控制，变化可能是疾病的信号。美国加州大学欧文分校的Cholon Jang和他的同事回顾了代谢物测量技术的发展，重点介绍了阐明代谢在疾病中的作用的关键研究。他们报告说，质谱学的最新进展允许同时测量数百种代谢物，将这些技术与标记的示踪剂分子相结合，可以揭示器官内特定的代谢物转化。未来的方向包括设计侵入性更小的方法，探索未知的代谢物，以及与其他数据整合，如基因组学。
Mammalian organs convert dietary nutrients into circulating metabolites and share them to maintain whole-body metabolic homeostasis. While the concentrations of circulating metabolites have been frequently measured in a variety of pathophysiological conditions, the exchange flux of circulating metabolites between organs is not easily measurable due to technical difficulties. Isotope tracing is useful for measuring such fluxes for a metabolite of interest, but the shuffling of isotopic atoms between metabolites requires mathematical modeling. Arteriovenous metabolite gradient measurements can complement isotope tracing to infer organ-specific net fluxes of many metabolites simultaneously. Here, we review the historical development of arteriovenous measurements and discuss their advantages and limitations with key example studies that have revealed metabolite exchange flux between organs in diverse pathophysiological contexts. Measuring concentrations of metabolites such as lipids or fatty acids in blood entering and exiting an organ reveals whether the organ uses or produces that metabolite. Organs convert food into metabolites, and specialize in producing different metabolites. These metabolites are then shared among organs; concentrations are tightly regulated, and changes can signal disease. Cholsoon Jang and coworkers at the University of California Irvine, USA have reviewed the development of techniques for measuring metabolites, highlighting key studies that illuminate metabolic roles in disease. They report that recent advances in mass spectrometry permit simultaneous measurement of hundreds of metabolites and that combining these techniques with labeled tracer molecules can reveal specific metabolite conversions within an organ. Future directions include designing less invasive methods, exploring unknown metabolites, and integration with other data, such as genomics.
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