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

GRK2 levels in myeloid cells modulate adipose-liver crosstalk in high fat diet-induced obesity. Cell Mol Life Sci. 2020 Jan 11;: Authors: Vila-Bedmar R, Cruces-Sande M, Arcones AC, Willemen HLDM, Prieto P, Moreno-Indias I, Díaz-Rodríguez D, Francisco S, Jaén RI, Gutiérrez-Repiso C, Heijnen CJ, Boscá L, Fresno M, Kavelaars A, Mayor F, Murga C 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. ...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research