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  IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis

Theurich, S., Tsaousidou, E., Hanssen, R., Lempradl, A. M., Mauer, J., Timper, K., et al. (2017). IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis. Cell Metabolism, 26, 171-184. doi:org/10.1016/j.cmet.2017.05.018.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0000-BF05-4 Version Permalink: https://hdl.handle.net/21.11116/0000-0008-99BE-6
Genre: Journal Article

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https://www.sciencedirect.com/science/article/pii/S155041311730342X (Publisher version)
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 Creators:
Theurich, Sebastian1, Author
Tsaousidou, Eva1, Author
Hanssen, Ruth1, Author
Lempradl, Adelheid M.2, Author
Mauer, Jan1, Author
Timper, Katharina1, Author
Schilbach, Katharina1, Author
Folz-Donahue, Kat1, Author
Heilinger, Christian1, Author
Sexl, Veronika1, Author
Pospisilik, John Andrew2, Author
Wunderlich, F. Thomas1, Author
Brüning, Jens C.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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 Abstract: Natural killer (NK) cells contribute to the development of obesity-associated insulin resistance. We demonstrate that in mice obesity promotes expansion of a distinct, interleukin-6 receptor (IL6R)a-expressing NK subpopulation, which also expresses a number of other myeloid lineage genes such as the colony-stimulating factor 1 receptor (Csf1r). Selective ablation of this Csf1r-expressing NK cell population prevents obesity and insulin resistance. Moreover, conditional inactivation of IL6Ra or Stat3 in NK cells limits obesity-associated formation of these myeloid signature NK cells, protecting from obesity, insulin resistance, and obesity-associated inflammation. Also in humans IL6Ra+ NK cells increase in obesity and correlate with markers of systemic low-grade inflammation, and their gene expression profile overlaps with characteristic gene sets of NK cells in obese mice. Collectively, we demonstrate that obesity-associated inflammation and metabolic disturbances depend on interleukin-6/Stat3-dependent formation of a distinct NK population, which may provide a target for the treatment of obesity, metaflammation-associated pathologies, and diabetes.

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Language(s): eng - English
 Dates: 2017-07-05
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: org/10.1016/j.cmet.2017.05.018
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Title: Cell Metabolism
  Other : Cell Metabolism
Source Genre: Journal
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Publ. Info: Cambridge, MA : Cell Press
Pages: - Volume / Issue: 26 Sequence Number: - Start / End Page: 171 - 184 Identifier: ISSN: 1550-4131
CoNE: https://pure.mpg.de/cone/journals/resource/111088195284928