期刊
JOURNAL OF NEUROENDOCRINOLOGY
卷 29, 期 12, 页码 -出版社
WILEY
DOI: 10.1111/jne.12546
关键词
hypothalamus; IL-6; IL-6R; tanycytes; third ventricle
资金
- Vetenskapsradet [K2016-54X-09894-19-3, 2015-02477]
- Johan och Jakob Soderbergs Foundation
- Marcus Borgstroms Foundation
- Nilsson-Ehle Foundation
- NovoNordisk Foundation
- Novo Nordisk Foundation Excellence Project Grant
- Inga-Britt och Arne Lundbergs Foundation
- Swedish Medical Society
- Swedish Society for Medical Research
- Kungl och Hvitfeldtska Foundation
- EC FP7 [Health-F2-2010-259772, 245009, Full4Health FP7-KBBE-2010-4-266408, 222720]
- Knut och Alice Wallenberg Foundation Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden
- Swedish Research Council [2015-02477] Funding Source: Swedish Research Council
- Novo Nordisk Fonden [NNF16OC0021214] Funding Source: researchfish
- Vinnova [2015-02477] Funding Source: Vinnova
Interleukin (IL)-6(-)/(-) mice develop mature onset obesity, whereas i.c.v. injection of IL-6 decreases obesity in rodents. Moreover, levels of IL-6 in cerebrospinal fluid (CSF) were reported to be inversely correlated with obesity in humans. Tanycytes lining the base of the third ventricle (3V) in the hypothalamus have recently been reported to be of importance for metabolism. In the present study, we investigated whether tanycytes could respond to IL-6 in the CSF. With immunohistochemistry using a well characterised antibody directed against the ligand binding receptor for IL-6, IL-6 receptor (IL-6R), it was found that tanycytes, identified by the two markers, vimentin and dopamine- and cAMP-regulated phosphoprotein of 32 kDa, contained IL-6R. There were fewer IL-6R on another type of ventricle-lining cells, ependymal cells, as identified by the marker glucose transporter-1. To demonstrate that the immunoreactive IL-6R were responsive to IL-6, we injected IL-6 i.c.v. This treatment increased immunoreactive phosphorylated signal transducer and activator of transcription-3 (pSTAT3) in tanycytes after 5minutes and in cells in the medial part of the arcuate nucleus after 5 and 15 minutes. Intracerebroventricular injection of leptin exerted similar effects. As expected, i.p. injection of leptin also induced pSTAT3 staining in the hypothalamus, whereas i.p. IL-6 injection had little effect on this parameter. Intracerebroventricular or i.p. injection of vehicle only had no effect on pSTAT3-immunoreactivity. In summary, there are functional IL-6R on tanycytes at the bottom of the 3V, in agreement with the possibility that ventricular administration of IL-6 decreases obesity in mice via an effect on this cell type.
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