title: Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity.
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.
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Byung-Cheol
authors.initials: BC
authors.lastname: Lee
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Korea Food Research Institute and University of Science and Technology (UST), Seongnam 463-746, Korea.
authors.forename: Myung-Sunny
authors.initials: MS
authors.lastname: Kim
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Munkyong
authors.initials: M
authors.lastname: Pae
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Delphine
authors.initials: D
authors.lastname: Eberlé
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimada
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kamei
authors.affiliation: Korea Food Research Institute and University of Science and Technology (UST), Seongnam 463-746, Korea.
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Park
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Souphatta
authors.initials: S
authors.lastname: Sasorith
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ju Rang
authors.initials: JR
authors.lastname: Woo
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: William
authors.initials: W
authors.lastname: Mosher
authors.affiliation: Department of Life Sciences, South Kensington Campus, Imperial College, London SW7 2AZ, UK.
authors.forename: Hugh J M
authors.initials: HJ
authors.lastname: Brady
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Shoelson
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: jongsoon.lee@joslin.harvard.edu.
authors.forename: Jongsoon
authors.initials: J
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000473:pathology*; D000818:Animals; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000473:pathology; D007333:Insulin Resistance; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications* / Q000276:immunology / Q000473:pathology