Spatially resolved isotope tracing reveals tissue metabolic activity.

TitleSpatially resolved isotope tracing reveals tissue metabolic activity.
Publication TypeJournal Article
Year of Publication2022
AuthorsWang, L, Xing, X, Zeng, X, S Jackson, RE, TeSlaa, T, Al-Dalahmah, O, Samarah, LZ, Goodwin, K, Yang, L, McReynolds, MR, Li, X, Wolff, JJ, Rabinowitz, JD, Davidson, SM
JournalNat Methods
Volume19
Issue2
Pagination223-230
Date Published2022 02
ISSN1548-7105
KeywordsAnimals, Brain, Carbon Isotopes, Diet, Enzymes, Gluconeogenesis, Glutamic Acid, Glycolysis, Kidney, Male, Mice, Inbred C57BL, Molecular Imaging, Nitrogen Isotopes, Single-Cell Analysis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tandem Mass Spectrometry, Tricarboxylic Acids, Workflow
Abstract

<p>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.</p>

DOI10.1038/s41592-021-01378-y
Alternate JournalNat Methods
PubMed ID35132243
Grant ListDP1 DK113643 / DK / NIDDK NIH HHS / United States
P30 CA072720 / CA / NCI NIH HHS / United States