Fgr kinase is required for proinflammatory macrophage activation during diet-induced obesity

Rebeca Acín-Pérez, Salvador Iborra, Yolanda Martí-Mateos, Emma C.L. Cook, Ruth Conde-Garrosa, Anton Petcherski, Mª ªM Muñoz, Raquel Martínez de Mena, Karthickeyan Chella Krishnan, Concepción Jiménez, Juan Pedro Bolaños, Markku Laakso, Aldon J. Lusis, Orian S. Shirihai, David Sancho, José Antonio Enríquez

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Proinflammatory macrophages are key in the development of obesity. In addition, reactive oxygen species (ROS), which activate the Fgr tyrosine kinase, also contribute to obesity. Here we show that ablation of Fgr impairs proinflammatory macrophage polarization while preventing high-fat diet (HFD)-induced obesity in mice. Systemic ablation of Fgr increases lipolysis and liver fatty acid oxidation, thereby avoiding steatosis. Knockout of Fgr in bone marrow (BM)-derived cells is sufficient to protect against insulin resistance and liver steatosis following HFD feeding, while the transfer of Fgr-expressing BM-derived cells reverts protection from HFD feeding in Fgr-deficient hosts. Scavenging of mitochondrial peroxides is sufficient to prevent Fgr activation in BM-derived cells and HFD-induced obesity. Moreover, Fgr expression is higher in proinflammatory macrophages and correlates with obesity traits in both mice and humans. Thus, our findings reveal the mitochondrial ROS–Fgr kinase as a key regulatory axis in proinflammatory adipose tissue macrophage activation, diet-induced obesity, insulin resistance and liver steatosis.

Original languageEnglish
Pages (from-to)974-988
Number of pages15
JournalNature Metabolism
Issue number9
StatePublished - 1 Sep 2020
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Cell Biology


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