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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Sample Preparation:

Sampleprep ID:SP002372
Sampleprep Summary:One million CD45+ F4/80+ CD11c+ FACS-sorted alveolar macrophages (AMs) from the bronchoalveolar lavage (BAL) of adult Tfamf/f and CD11c∆Tfam mice were collected. Each sample was generated by merging FACS-sorted AMs from 13 to 30 mice. Quality Control (QC) samples (n=4) were prepared by pooling equal volumes of cell extracts from each sample by following the same protocols used for the subject samples. Samples were subjected to two freeze–thaw cycles for metabolism quenching and complete metabolite extraction, specifically by placing the samples at -80ºC for 15 min and thawing them on ice for 10 min with brief vortex-mixing. The samples were then centrifuged at 20,000 xg at 4°C for 10 min and the supernatant collected. The supernatant was evaporated to dryness (SpeedVac Concentrator, Thermo Fisher Scientific, Waltham, MA, USA) and derivatized with 10 μl O-methoxyamine hydrochloride (15mg/mL) in pyridine and 10 μl N,O-bis(trimethylsilyl)trifluoroacetamide in 1% trimethylchlorosilane. Finally, 100 μl of heptane containing 10 ppm of 4-nitrobenzoic acid (IS) was used as internal standard to monitor sample injection
Sampleprep Protocol Filename:Protocol_AM.pdf
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