Journal
NATURE METABOLISM
Volume 2, Issue 9, Pages 974-+Publisher
NATURE RESEARCH
DOI: 10.1038/s42255-020-00273-8
Keywords
-
Categories
Funding
- Academy of Finland [321428]
- Sigrid Juselius Foundation
- Finnish Foundation for Cardiovascular Research
- Academy of Finland
- Agencia Estatal de Investigacion (AEI)
- Fondo Europeo de Desarrollo Regional (FEDER) [SAF2015-65633-R, RTI2018099357-B-I00]
- EU [UE0/MCA317433]
- Biomedical Research Networking Center on Frailty and Healthy Ageing (CIBERFES-ISCiii)
- HFSP agency [RGP0016/2018]
- Ministerio de Ciencia, Innovacion e Universidades (MICINN)
- CNIC
- European Research Council [725091]
- European Commission [635122-PROCROP H2020]
- MICINN
- AEI
- FEDER [SAF2016-79040-R, PID2019-108157RB, RD16/0015/0018-REEM]
- Comunidad de Madrid [B2017/BMD-3733 Immunothercan-CM]
- FIS-Instituto de Salud Carlos III
- Acteria Foundation
- Atresmedia
- Fundacio La Marato de TV3 [201723]
- National Institutes of Health (NIH) [R01 DK099618-05, R01 CA232056-01, R21AG060456-01, R21 AG063373-01]
- American Diabetes Association [1-19-IBS-049]
- Spanish Ministry of Science, Innovation and Universities (MCINU/FEDER) [SAF2016-78114-R, RED2018-102576-T]
- Instituto de Salud Carlos III [CB16/10/00282]
- Junta de Castilla y Leon (Escalera de Excelencia) [CLU-2017-03]
- Ayudas Equipos Investigacion Biomedicina 2017 Fundacion BBVA
- Fundacion Ramon Areces
- Instituto de Salud Carlos III (ISCIII)
- Pro CNIC Foundation
- AHA [18POST33990256]
- Centre of Excellence of Cardiovascular and Metabolic Diseases
- [NIH-PO1HL028481]
- [NIH-R01DK117850]
- [NIH-K99 DK120875]
- [RYC-2016-19463]
- [RTI2018-094484-B-I00]
- European Research Council (ERC) [725091] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available