2026-05-04T18:39:34Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/182112024-09-27T07:55:50Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Wculek, Stefanie K author Heras-Murillo, Ignacio author Mastrangelo, Annalaura author Mañanes, Diego author Galán, Miguel author Miguel, Verónica author Curtabbi, Andrea author Barbas, Coral author Chandel, Navdeep S author Enriquez, Jose Antonio author Lamas, Santiago author Sancho, David author 2023-03-14 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. Immunity. 2023 Mar 14;56(3):516-530.e9. 10.1016/j.immuni.2023.01.011 1097-4180 Immunity 36738738 http://hdl.handle.net/20.500.12105/18211 Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis.