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

Felix M. Wensveen, Vedrana Jelenčić, Sonja Valentić, Marko Šestan, Tamara Turk Wensveen, Sebastian Theurich, Ariella Glasner, Davor Mendrila, Davor Štimac, F. Thomas Wunderlich, Jens C. Brüning, Ofer Mandelboim, Bojan Polić*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

376 Scopus citations


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.

Original languageAmerican English
Pages (from-to)376-385
Number of pages10
JournalNature Immunology
Issue number4
StatePublished - 19 Mar 2015

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