小柯机器人

近日，美国普林斯顿大学Shawn M. Davidson团队利用空间分辨的同位素示踪揭示组织代谢活性。相关论文于2022年2月7日在线发表在《自然—方法学》杂志上。

研究人员将稳定同位素标记的营养液输注与基质辅助激光解吸电离成像质谱法（iso-imaging）结合起来，以空间分辨率的方式对哺乳动物组织的代谢活动进行了定量。在肾脏中，研究人员分别对皮质和髓质中的葡萄糖生成通量和糖酵解通量进行可视化。三羧酸循环底物的使用在不同的肾脏区域有所不同；谷氨酰胺和柠檬酸盐在皮质中被优先使用，脂肪酸在髓质中被使用。

在大脑中，研究人员观察到在生酮饮食下，三羧酸循环和谷氨酸的碳输入在空间上的梯度。在富含碳水化合物的饮食中，葡萄糖占主导地位，但在生酮饮食中，3-羟基丁酸在海马区的贡献最大，在中脑的贡献最小。大脑的氮源在空间上也有差异；支链氨基酸在中脑的贡献最大，而氨在丘脑的贡献最大。因此，同位素成像可以揭示代谢活动的空间组织。

据悉，同位素追踪有助于确定器官的代谢活动。探测器官内代谢异质性的方法还不太成熟。

附：英文原文

Title: Spatially resolved isotope tracing reveals tissue metabolic activity

Author: Wang, Lin, Xing, Xi, Zeng, Xianfeng, Jackson, S. RaElle, TeSlaa, Tara, Al-Dalahmah, Osama, Samarah, Laith Z., Goodwin, Katharine, Yang, Lifeng, McReynolds, Melanie R., Li, Xiaoxuan, Wolff, Jeremy J., Rabinowitz, Joshua D., Davidson, Shawn M.

Issue&Volume: 2022-02-07

Abstract: Isotope tracing has helped to determine the metabolic activities of organs. Methods to probe metabolic heterogeneity within organs are less developed. We couple stable-isotope-labeled nutrient infusion to matrix-assisted laser desorption ionization imaging mass spectrometry (iso-imaging) to quantitate metabolic activity in mammalian tissues in a spatially resolved manner. In the kidney, we visualize gluconeogenic flux and glycolytic flux in the cortex and medulla, respectively. Tricarboxylic acid cycle substrate usage differs across kidney regions; glutamine and citrate are used preferentially in the cortex and fatty acids are used in the medulla. In the brain, we observe spatial gradations in carbon inputs to the tricarboxylic acid cycle and glutamate under a ketogenic diet. In a carbohydrate-rich diet, glucose predominates throughout but in a ketogenic diet, 3-hydroxybutyrate contributes most strongly in the hippocampus and least in the midbrain. Brain nitrogen sources also vary spatially; branched-chain amino acids contribute most in the midbrain, whereas ammonia contributes in the thalamus. Thus, iso-imaging can reveal the spatial organization of metabolic activity. Iso-imaging integrates stable-isotope infusions with imaging mass spectrometry to enable quantitative analysis of metabolic activity in mammalian tissues with spatial resolution. IsoScope software facilitates analysis of iso-imaging data.

DOI: 10.1038/s41592-021-01378-y

Source: https://www.nature.com/articles/s41592-021-01378-y

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex