Universität zu Köln

Theurich, Sebastian ORCID: 0000-0001-5706-8258, Tsaousidou, Eva ORCID: 0000-0003-2751-1911, Hanssen, Ruth, Lempradl, Adelheid M., Mauer, Jan ORCID: 0000-0002-0189-5876, Timper, Katharina, Schilbach, Katharina, Folz-Donahue, Kat, Heilinger, Christian, Sexl, Veronika ORCID: 0000-0001-9363-0412, Pospisilik, John Andrew, Wunderlich, F. Thomas and Bruening, Jens C. (2017). IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis. Cell Metab., 26 (1). S. 171 - 191. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Theurich, Sebastian UNSPECIFIED orcid.org/0000-0001-5706-8258 UNSPECIFIED Tsaousidou, Eva UNSPECIFIED orcid.org/0000-0003-2751-1911 UNSPECIFIED Hanssen, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Lempradl, Adelheid M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauer, Jan UNSPECIFIED orcid.org/0000-0002-0189-5876 UNSPECIFIED Timper, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Schilbach, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Folz-Donahue, Kat UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilinger, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Sexl, Veronika UNSPECIFIED orcid.org/0000-0001-9363-0412 UNSPECIFIED Pospisilik, John Andrew UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-225143
DOI:	10.1016/j.cmet.2017.05.018
Journal or Publication Title:	Cell Metab.
Volume:	26
Number:	1
Page Range:	S. 171 - 191
Date:	2017
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1932-7420
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INNATE LYMPHOID-CELLS; NATURAL-KILLER-CELLS; WHITE ADIPOSE-TISSUE; INSULIN-RESISTANCE; SKELETAL-MUSCLE; IN-VIVO; MACROPHAGES; IL-6; INFLAMMATION; ACTIVATION Multiple languages Cell Biology; Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22514