Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity
File(s)
Accepted version
Accepted version
Author(s)
Type
Journal Article
Abstract
Obesity-induced inflammation mediated by immune cells in adipose tissue appears to participate in the pathogenesis of insulin resistance. We show that natural killer (NK) cells in adipose tissue play an important role. High-fat diet (HFD) increases NK cell numbers and the production of proinflammatory cytokines, notably TNFα, in epididymal, but not subcutaneous, fat depots. When NK cells were depleted either with neutralizing antibodies or genetic ablation in E4bp4+/− mice, obesity-induced insulin resistance improved in parallel with decreases in both adipose tissue macrophage (ATM) numbers, and ATM and adipose tissue inflammation. Conversely, expansion of NK cells following IL-15 administration or reconstitution of NK cells into E4bp4−/− mice increased both ATM numbers and adipose tissue inflammation and exacerbated HFD-induced insulin resistance. These results indicate that adipose NK cells control ATMs as an upstream regulator potentially by producing proinflammatory mediators, including TNFα, and thereby contribute to the development of obesity-induced insulin resistance.
Date Issued
2016-03-31
Date Acceptance
2016-03-04
Citation
Cell Metabolism, 2016, 23 (4), pp.685-698
ISSN
1932-7420
Publisher
Elsevier
Start Page
685
End Page
698
Journal / Book Title
Cell Metabolism
Volume
23
Issue
4
Copyright Statement
© 2016 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Medical Research Council (MRC)
Grant Number
G0901737
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Endocrinology & Metabolism
NECROSIS-FACTOR-ALPHA
T-CELLS
NK CELLS
IMMUNE-RESPONSE
INFLAMMATION
SUBSETS
E4BP4
ACCUMULATION
HOMEOSTASIS
ACTIVATION
0601 Biochemistry And Cell Biology
1101 Medical Biochemistry And Metabolomics
Publication Status
Published