Timper, Katharina, Denson, Jesse Lee, Steculorum, Sophie Marie, Heilinger, Christian, Engstroem-Ruud, Linda, Wunderlich, Claudia Maria, Rose-John, Stefan ORCID: 0000-0002-7519-3279, Wunderlich, F. Thomas and Bruening, Jens Claus (2017). IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling. Cell Reports, 19 (2). S. 267 - 281. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Interleukin (IL)-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R) expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH) of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Timper, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denson, Jesse LeeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steculorum, Sophie MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heilinger, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engstroem-Ruud, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, Claudia MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rose-John, StefanUNSPECIFIEDorcid.org/0000-0002-7519-3279UNSPECIFIED
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-234000
DOI: 10.1016/j.celrep.2017.03.043
Journal or Publication Title: Cell Reports
Volume: 19
Number: 2
Page Range: S. 267 - 281
Date: 2017
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NECROSIS-FACTOR-ALPHA; INSULIN ACTION; ADIPOSE-TISSUE; HEPATIC INFLAMMATION; CEREBROSPINAL-FLUID; INTERLEUKIN-6 IL-6; LEPTIN RESISTANCE; SKELETAL-MUSCLE; GENE KNOCKOUT; SOLUBLE FORMSMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23400

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