Summary of Study ST002280

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 PR001460. The data can be accessed directly via it's Project DOI: 10.21228/M80T4P This work is supported by NIH grant, U2C- DK119886.

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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 IDST002280
Study TitleOxidative phosphorylation selectively orchestrates tissue macrophage homeostasis
Study TypeObservational study
Study SummaryIn vitro studies associated oxidative phosphorylation (OXPHOS) with anti-inflammatory macrophages, while pro-inflammatory macrophages rely on glycolysis. However, the metabolic needs of macrophages in tissues (TMFs) to fulfil their homeostatic activities are incompletely understood. Here, we identified OXPHOS as highly discriminating process among TMFs from different tissues in homeostasis by analysis of RNAseq data, in both human and mouse. Impairing OXPHOS in TMFs via Tfam deletion differentially affected TMF populations. Tfam deletion resulted in reduction of alveolar macrophages (AMs) due to impaired lipid-handling capacity, leading to increased cholesterol content and cellular stress, causing cell cycle arrest in vivo. In obesity, Tfam depletion selectively ablated pro-inflammatory lipid-handling white adipose tissue macrophages (WAT-MFs), preventing insulin resistance and hepatosteatosis. Thus, OXPHOS, rather than glycolysis, distinguishes TMF populations and is critical for the maintenance of TMFs with a high lipid-handling activity, including pro-inflammatory WAT-MFs. This could provide a selective therapeutic targeting tool.
Institute
Spanish National Center for Cardiovascular Research (CNIC)
DepartmentNovel mechanisms of atherosclerosis
LaboratoryImmunobiology
Last NameMastrangelo
First NameAnnalaura
AddressCalle de Melchor Fernández Almagro, 3, Centro Nacional de Investigaciones Cardiovasculares
Emailannalaura.mastrangelo@cnic.es
Phone(+34) 914531200
Submit Date2022-09-01
Num Groups2
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailGC-MS
Release Date2022-09-22
Release Version1
Annalaura Mastrangelo Annalaura Mastrangelo
https://dx.doi.org/10.21228/M80T4P
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN003724
Analysis type MS
Chromatography type GC
Chromatography system Agilent 7890B
Column Agilent DB5-MS (30m x 0.25mm, 0.25um)
MS Type EI
MS instrument type QTOF
MS instrument name Agilent 7250 GC/Q-TOF
Ion Mode POSITIVE
Units relative abundance

MS:

MS ID:MS003472
Analysis ID:AN003724
Instrument Name:Agilent 7250 GC/Q-TOF
Instrument Type:QTOF
MS Type:EI
MS Comments:The EI source was operated at 70 eV whereas the mass spectrometer operated in the scan mode over a mass range of m/z 50–600. Metabolite deconvolution and identification were carried out using Agilent MassHunter Unknowns Analysis version B.07.00, then, data was aligned in Agilent Mass Profiler Professional version B.12.1 and exported to Agilent MassHunter Quantitative Analysis version B.07.00. Metabolites were identified by comparing their retention time, retention index and mass fragmentation patterns with those available in an in-house library including both the NIST mass spectral database (version 2017) and Fiehn RTL library (version 2008). The different derivatives that were generated from the silylated compounds were unified by summing the abundance of all derivatives from the same metabolite. Finally, the median relative area of the two analytical replicates of the same sample was computed and used for subsequent statistical analysis.
Ion Mode:POSITIVE
Analysis Protocol File:Protocol_AM.pdf
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