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Title

GRK2 levels in myeloid cells modulate adipose-liver crosstalk in high fat diet-induced obesity

AuthorsVila-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; Heijnen, Cobi J.; Boscá, Lisardo ; Fresno, Manuel ; Kavelaars, Annemieke; Mayor Jr., Federico; Murga, Cristina
Issue Date2020
PublisherSpringer Nature
CitationCellular and Molecular Life Sciences: (2020)
AbstractMacrophages 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.
Publisher version (URL)https://doi.org/10.1007/s00018-019-03442-5
URIhttp://hdl.handle.net/10261/222197
DOI10.1007/s00018-019-03442-5
ISSN1420-682X
E-ISSN1420-9071
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