Summary of Study ST002219

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001417. The data can be accessed directly via it's Project DOI: 10.21228/M8JX39 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002219
Study TitleSpatially resolved characterization of tissue metabolic compartments in fasted and high-fat diet livers
Study SummaryCells adapt their metabolism to physiological stimuli, and metabolic heterogeneity exists between cell types, within tissues, and subcellular compartments. The liver plays an essential role in maintaining whole-body metabolic homeostasis and is structurally defined by metabolic zones. These zones are well-understood on the transcriptomic level, but have not been comprehensively characterized on the metabolomic level. Mass spectrometry imaging (MSI) can be used to map hundreds of metabolites directly from a tissue section, offering an important advance to investigate metabolic heterogeneity in tissues compared to extraction-based metabolomics methods that analyze tissue metabolite profiles in bulk. We established a workflow for the preparation of tissue specimens for matrix-assisted laser desorption/ionization (MALDI) MSI that can be implemented to achieve broad coverage of central carbon, nucleotide, and lipid metabolism pathways. Herein, we used this approach to visualize the effect of nutrient stress and excess on liver metabolism. Our data revealed a highly organized metabolic tissue compartmentalization in livers, which becomes disrupted under high fat diet. Fasting caused changes in the abundance of several metabolites, including increased levels of fatty acids and TCA intermediates while fatty livers had higher levels of purine and pentose phosphate-related metabolites, which generate reducing equivalents to counteract oxidative stress. This spatially conserved approach allowed the visualization of liver metabolic compartmentalization at 30 µm pixel resolution and can be applied more broadly to yield new insights into metabolic heterogeneity in vivo.
Institute
Brigham and Women's Hospital
DepartmentBrigham and Women's Hospital
Last NameStopka
First NameSylwia
Address60 Fenway Rd
Emailsstopka@bwh.harvard.edu
Phone617-525-9746
Submit Date2022-05-12
Raw Data AvailableYes
Raw Data File Type(s)imzML
Analysis Type DetailMALDI-MS
Release Date2022-08-18
Release Version1
Sylwia Stopka Sylwia Stopka
https://dx.doi.org/10.21228/M8JX39
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Collection:

Collection ID:CO002298
Collection Summary:C57BL/6J (000664) and BALB/cJ (000651) mice were obtained from The Jackson Laboratory. Mice were housed at 20-22°C on a 12 h light/dark cycle with ad libitum access to food (PicoLab Rodent Diet 5053) and water. All animal studies were performed in accordance with Haigis lab protocols approved by the Standing Committee on Animals, the Institutional Animal Care and Use Committee at Harvard Medical School. For heat inactivation studies, 3 mice were used (C57BL/6J, female, 7 weeks old) and kidneys, brain halves, and liver lobes from the same individual animal were subjected to the different heat inactivation treatments (overview in Supplementary Fig. 1A, E). For desiccation experiments, 2 mice were used (C57BL/6J, male, 7 weeks old). For fasting experiments, two independent cohorts of 5 mice were used per treatment group (BALB/cJ, female, 10-11 weeks old) and mice were subjected to a 16 hour overnight fast. For HFD experiments, two independent cohorts of 4 mice were used per treatment group (C57BL/6J, female). Mice were assigned at 5 weeks old to the control diet (PicoLab Rodent Diet 5053) or HFD (Research Diets, Inc. #12492) and maintained on this diet for 4.5 months. The control diet is 4.07 Gross Energy Kcal/g. The HFD is 5.21 Kcal/g. for 8-10 weeks. Comparative MALDI MSI and LC-MS analyses of tissues were always performed on the same tissue specimens.
Sample Type:Liver_Brain_Kidney
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