GRK2 levels in myeloid cells modulate adipose-liver crosstalk in high fat diet-induced obesity
Publication date
2020-12
Authors
Vila-Bedmar, Rocío
Cruces-Sande, Marta
Arcones, Alba C
Willemen, Hanneke L D M
Prieto, Patricia
Moreno-Indias, Isabel
Díaz-Rodríguez, Daniel
Francisco, Sara
Jaén, Rafael I
Gutiérrez-Repiso, Carolina
Editors
Advisors
Supervisors
Document Type
Article
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License
taverne
Abstract
Macrophages are key effector cells in obesity-associated inflammation. G protein-coupled receptor kinase 2 (GRK2) is highly expressed in different immune cell types. Using LysM-GRK2+/- mice, we uncover that a reduction of GRK2 levels in myeloid cells prevents the development of glucose intolerance and hyperglycemia after a high fat diet (HFD) through modulation of the macrophage pro-inflammatory profile. Low levels of myeloid GRK2 confer protection against hepatic insulin resistance, steatosis and inflammation. In adipose tissue, pro-inflammatory cytokines are reduced and insulin signaling is preserved. Macrophages from LysM-GRK2+/- mice secrete less pro-inflammatory cytokines when stimulated with lipopolysaccharide (LPS) and their conditioned media has a reduced pathological influence in cultured adipocytes or naïve bone marrow-derived macrophages. Our data indicate that reducing GRK2 levels in myeloid cells, by attenuating pro-inflammatory features of macrophages, has a relevant impact in adipose-liver crosstalk, thus preventing high fat diet-induced metabolic alterations.
Keywords
Adipose tissue, GRK2, Glucose homeostasis, Liver, Macrophages, Obesity, Cytoprotection/drug effects, Myeloid Cells/drug effects, Fatty Liver/complications, G-Protein-Coupled Receptor Kinase 2/metabolism, Glucose Intolerance/metabolism, Adipose Tissue/metabolism, Diet, High-Fat, Liver/metabolism, Insulin/metabolism, Gastrointestinal Microbiome/drug effects, Glucose/metabolism, Adipose Tissue, White/pathology, Inflammation/pathology, Mice, Inbred C57BL, Insulin Resistance, Macrophages, Peritoneal/drug effects, Signal Transduction/drug effects, Adipocytes/drug effects, Animals, Culture Media, Conditioned/pharmacology, Models, Biological, Obesity/complications, Weight Gain/drug effects, Hypertrophy, Taverne, Cellular and Molecular Neuroscience, Molecular Medicine, Molecular Biology, Cell Biology, Pharmacology, Journal Article
Citation
Vila-Bedmar, R, Cruces-Sande, M, Arcones, A C, Willemen, H L D M, Prieto, P, Moreno-Indias, I, Díaz-Rodríguez, D, Francisco, S, Jaén, R I, Gutiérrez-Repiso, C, Heijnen, C J, Boscá, L, Fresno, M, Kavelaars, A, Mayor, F & Murga, C 2020, 'GRK2 levels in myeloid cells modulate adipose-liver crosstalk in high fat diet-induced obesity', Cellular and Molecular Life Sciences, vol. 77, no. 23, pp. 4957-4976. https://doi.org/10.1007/s00018-019-03442-5