Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis
- PMID: 36738738
- DOI: 10.1016/j.immuni.2023.01.011
Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis
Abstract
In vitro studies have associated oxidative phosphorylation (OXPHOS) with anti-inflammatory macrophages, whereas pro-inflammatory macrophages rely on glycolysis. However, the metabolic needs of macrophages in tissues (TMFs) to fulfill their homeostatic activities are incompletely understood. Here, we identified OXPHOS as the highest discriminating process among TMFs from different organs in homeostasis by analysis of RNA-seq data in both humans and mice. 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), thus preventing insulin resistance and hepatosteatosis. Hence, 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.
Keywords: Tfam; cholesterol handling; immunometabolism; obesity; oxidative phosphorylation; pro-inflammatory macrophages; tissue macrophages.
Copyright © 2023 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests The authors declare no competing interests.
Comment in
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Tissue differences in macrophage metabolism.Nat Immunol. 2023 Mar;24(3):378. doi: 10.1038/s41590-023-01459-4. Nat Immunol. 2023. PMID: 36829074 No abstract available.
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