Spatial isotope deep tracing deciphers inter-tissue metabolic crosstalk

Xinzhu Li, Ying Zhu, Ting Li, Xinyi Tu, Shiyu Zhu, Lingzhi Wang, Fei Li, Chenglong Sun, Xin Li, Haiyi Zhao, Tang Tang, Qingce Zang (), Ruiping Zhang () and Zeper Abliz ()
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Xinzhu Li: Chinese Academy of Medical Sciences and Peking Union Medical College
Ying Zhu: Chinese Academy of Medical Sciences and Peking Union Medical College
Ting Li: Chinese Academy of Medical Sciences and Peking Union Medical College
Xinyi Tu: Chinese Academy of Medical Sciences and Peking Union Medical College
Shiyu Zhu: Chinese Academy of Medical Sciences and Peking Union Medical College
Lingzhi Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Fei Li: Chinese Academy of Medical Sciences and Peking Union Medical College
Chenglong Sun: Qilu University of Technology (Shandong Academy of Sciences)
Xin Li: Chinese Academy of Medical Sciences and Peking Union Medical College
Haiyi Zhao: Ltd
Tang Tang: Ltd
Qingce Zang: Chinese Academy of Medical Sciences and Peking Union Medical College
Ruiping Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Zeper Abliz: Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Organs collaborate to maintain metabolic homeostasis in mammals. Spatial metabolomics makes strides in profiling the metabolic landscape, yet can not directly inspect the metabolic crosstalk between tissues. Here, we introduce an approach to comprehensively trace the metabolic fate of 13C-nutrients within the body and present a robust computational tool, MSITracer, to deep-probe metabolic activity in a spatial manner. By discerning spatial distribution differences between isotopically labeled metabolites from ambient mass spectrometry imaging-based isotope tracing data, this approach empowers us to characterize fatty acid metabolic crosstalk between the liver and heart, as well as glutamine metabolic exchange across the kidney, liver, and brain. Moreover, we disclose that tumor burden significantly influences the host’s hexosamine biosynthesis pathway, and that the glucose-derived glutamine released from the lung as a potential source for tumor glutamate synthesis. The developed approach facilitates the systematic characterization of metabolic activity in situ and the interpretation of tissue metabolic communications in living organisms.

Date: 2025
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DOI: 10.1038/s41467-025-63243-2

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