학술논문
Fgr kinase is required for proinflammatory macrophage activation during diet-induced obesity.
Document Type
Academic Journal
Author
Acín-Pérez R; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.; Iborra S; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense, Madrid, Spain.; Martí-Mateos Y; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Cook ECL; Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense, Madrid, Spain.; Conde-Garrosa R; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Petcherski A; Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.; Muñoz MDM; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Martínez de Mena R; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Krishnan KC; Department of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, USA.; Jiménez C; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Bolaños JP; Institute of Functional Biology and Genomics, University of Salamanca, CSIC, Salamanca, Spain.; Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Salamanca, Spain.; Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain.; Laakso M; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.; Lusis AJ; Department of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, USA.; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.; Shirihai OS; Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.; Sancho D; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. dsancho@cnic.es.; Enríquez JA; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. jaenriquez@cnic.es.; Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain. jaenriquez@cnic.es.
Source
Publisher: Springer Nature Country of Publication: Germany NLM ID: 101736592 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2522-5812 (Electronic) Linking ISSN: 25225812 NLM ISO Abbreviation: Nat Metab Subsets: MEDLINE
Subject
Language
English
Abstract
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.