@article{2618, keywords = {Animals, Male, Gluconeogenesis, Diet, Mice, Inbred C57BL, Carbon Isotopes, Glycolysis, Brain, Tandem Mass Spectrometry, Enzymes, Kidney, Single-Cell Analysis, Nitrogen Isotopes, Glutamic Acid, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Molecular Imaging, Tricarboxylic Acids, Workflow}, author = {Lin Wang and Xi Xing and Xianfeng Zeng and RaElle Jackson and Tara TeSlaa and Osama Al-Dalahmah and Laith Samarah and Katharine Goodwin and Lifeng Yang and Melanie McReynolds and Xiaoxuan Li and Jeremy Wolff and Joshua Rabinowitz and Shawn Davidson}, title = {Spatially resolved isotope tracing reveals tissue metabolic activity.}, 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.
}, year = {2022}, journal = {Nat Methods}, volume = {19}, pages = {223-230}, month = {02/2022}, issn = {1548-7105}, doi = {10.1038/s41592-021-01378-y}, language = {eng}, }