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Nat Immunol. 2015 Apr;16(4):376-85. doi: 10.1038/ni.3120. Epub 2015 Mar 2.

NK cells link obesity-induced adipose stress to inflammation and insulin resistance.

Author information

1
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
2
Department of Internal Medicine, University Hospital Rijeka, Rijeka, Croatia.
3
Max Planck Institute for Metabolism Research Cologne, Cologne, Germany.
4
The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
5
Department of Surgery, University Hospital Rijeka, Rijeka, Croatia.

Abstract

An important cause of obesity-induced insulin resistance is chronic systemic inflammation originating in visceral adipose tissue (VAT). VAT inflammation is associated with the accumulation of proinflammatory macrophages in adipose tissue, but the immunological signals that trigger their accumulation remain unknown. We found that a phenotypically distinct population of tissue-resident natural killer (NK) cells represented a crucial link between obesity-induced adipose stress and VAT inflammation. Obesity drove the upregulation of ligands of the NK cell-activating receptor NCR1 on adipocytes; this stimulated NK cell proliferation and interferon-γ (IFN-γ) production, which in turn triggered the differentiation of proinflammatory macrophages and promoted insulin resistance. Deficiency of NK cells, NCR1 or IFN-γ prevented the accumulation of proinflammatory macrophages in VAT and greatly ameliorated insulin sensitivity. Thus NK cells are key regulators of macrophage polarization and insulin resistance in response to obesity-induced adipocyte stress.

PMID:
25729921
DOI:
10.1038/ni.3120
[Indexed for MEDLINE]

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