Home | NK cells link obesity-induced adipose stress to inflammation and insulin resistance
NK cells link obesity-induced adipose stress to inflammation and insulin resistance
A5 BRÜNING/NIESSENpublicationsWensveen FM, Jelen?i? V, Valenti? S, Šestan M, Wensveen TT, Theurich S, Glasner A, Mendrila D, Štimac D, Wunderlich FT, Brüning JC, Mandelboim O, Poli? B; Nat Immunol. 2015 Apr;16(4):376-85. doi: 10.1038/ni.3120. Epub 2015 Mar 2.
An important cause of obesity-inducedinsulinresistance 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-inducedadiposestress 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-? (IFN-?) production, which in turn triggered the differentiation of proinflammatory macrophages and promoted insulinresistance. Deficiency of NKcells, NCR1 or IFN-? prevented the accumulation of proinflammatory macrophages in VAT and greatly ameliorated insulin sensitivity. Thus NKcells are key regulators of macrophage polarization and insulinresistance in response to obesity-induced adipocyte stress.