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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Project:

Project ID:PR001460
Project DOI:doi: 10.21228/M80T4P
Project Title:Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis
Project Summary:In 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)
Department:Novel mechanisms of atherosclerosis
Laboratory:Immunobiology
Last Name:Mastrangelo
First Name:Annalaura
Address:Calle de Melchor Fernández Almagro, 3, Centro Nacional de Investigaciones Cardiovasculares
Email:annalaura.mastrangelo@cnic.es
Phone:(+34) 914531200
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