Spatially resolved isotope tracing reveals tissue metabolic activity

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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)223-230
Number of pages8
JournalNature Methods
Volume19
Issue number2
DOIs
StatePublished - Feb 2022

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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