Universität zu Köln

Xu, Elaine, Pereira, Mafalda M. A., Karakasilioti, Ismene, Theurich, Sebastian ORCID: 0000-0001-5706-8258, Al-Maarri, Mona, Rappl, Gunter, Waisman, Ari ORCID: 0000-0003-4304-8234, Wunderlich, F. Thomas and Bruening, Jens C. (2017). Temporal and tissue-specific requirements for T-lymphocyte IL-6 signalling in obesity-associated inflammation and insulin resistance. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Low-grade inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells. Interleukin-6 (IL-6) is a crucial regulator of T cells and is increased in obesity. Here we report that classical IL-6 signalling in T cells promotes inflammation and insulin resistance during the first 8 weeks on a high-fat diet (HFD), but becomes dispensable at later stages (after 16 weeks). Mice with T cell-specific deficiency of IL-6 receptor-alpha (IL-6R alpha(T-KO)) exposed to a HFD display improved glucose tolerance, insulin sensitivity and inflammation in liver and EWATafter 8 weeks. However, after 16 weeks, insulin resistance in IL-6R alpha(T-KO) epididymal white adipose tissue (EWAT) is comparable to that of controls, whereas the inflammatory profile is significantly worse. This coincided with a shift from classical T cell IL-6 signalling at 8 weeks, to enhanced IL-6 trans-signalling at 16 weeks. Collectively, our studies reveal that IL-6 action in T cells through classical IL-6 signalling promotes inflammation and insulin resistance early during obesity development, which can be compensated for by enhanced IL-6 trans-signalling at later stages.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Xu, Elaine UNSPECIFIED UNSPECIFIED UNSPECIFIED Pereira, Mafalda M. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Karakasilioti, Ismene UNSPECIFIED UNSPECIFIED UNSPECIFIED Theurich, Sebastian UNSPECIFIED orcid.org/0000-0001-5706-8258 UNSPECIFIED Al-Maarri, Mona UNSPECIFIED UNSPECIFIED UNSPECIFIED Rappl, Gunter UNSPECIFIED UNSPECIFIED UNSPECIFIED Waisman, Ari UNSPECIFIED orcid.org/0000-0003-4304-8234 UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-231389
DOI:	10.1038/ncomms14803
Journal or Publication Title:	Nat. Commun.
Volume:	8
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SOLUBLE INTERLEUKIN-6 RECEPTOR; FATTY LIVER-DISEASE; ADIPOSE-TISSUE; IN-VIVO; METABOLIC DISEASE; INTERFERON-GAMMA; CELLS; MICE; MACROPHAGES; ACTIVATION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23138