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Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis

ABSTRACT: 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.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Epithelial Lining Fluid

DISEASE(S): Inflammation

SUBMITTER: Annalaura Mastrangelo

PROVIDER: ST002280 | MetabolomicsWorkbench | Thu Sep 01 00:00:00 BST 2022

REPOSITORIES: MetabolomicsWorkbench

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Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis

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