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

Rocío Vila-Bedmar, Marta Cruces-Sande, Alba C. Arcones, Hanneke L.D.M. Willemen, Patricia Prieto, Isabel Moreno-Indias, Daniel Díaz-Rodríguez, Sara Francisco, Rafael I. Jaén, Carolina Gutiérrez-Repiso, Cobi J. Heijnen, Lisardo Boscá, Manuel Fresno, Annemieke Kavelaars, Federico Mayor, Cristina Murga

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4957-4976
Number of pages20
JournalCellular and Molecular Life Sciences
Volume77
Issue number23
DOIs
StatePublished - Dec 2020

Keywords

  • Adipose tissue
  • GRK2
  • Glucose homeostasis
  • Liver
  • Macrophages
  • Obesity

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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