Interleukin-6 in the central amygdala is bioactive and co-localised with glucagon-like peptide-1 receptor

Fredrik Anesten, Adrià Dalmau Gasull, Jennifer E. Richard, Imre Farkas, Devesh Mishra, Lilly Taing, Fuping Zhang, Matti Poutanen, Vilborg Palsdottir, Z. Liposits, Karolina P. Skibicka, John Olov Jansson

Research output: Contribution to journalArticle

Abstract

Neuronal circuits involving the central amygdala (CeA) are gaining prominence as important centres for regulation of metabolic functions. As a part of the subcortical food motivation circuitry, CeA is associated with food motivation and hunger. We have previously shown that interleukin (IL)-6 can act as a downstream mediator of the metabolic effects of glucagon-like peptide-1 (GLP-1) receptor (R) stimulation in the brain, although the sites of these effects are largely unknown. In the present study, we used the newly generated and validated RedIL6 reporter mouse strain to investigate the presence of IL-6 in the CeA, as well as possible interactions between IL-6 and GLP-1 in this nucleus. IL-6 was present in the CeA, mostly in cells in the medial and lateral parts of this structure, and a majority of IL-6-containing cells also co-expressed GLP-1R. Triple staining showed GLP-1 containing fibres co-staining with synaptophysin close to or overlapping with IL-6 containing cells. GLP-1R stimulation enhanced IL-6 mRNA levels. IL-6 receptor-alpha (IL-6Rα) was found to a large part in neuronal CeA cells. Using electrophysiology, we determined that cells with neuronal properties in the CeA could be rapidly stimulated by IL-6 administration in vitro. Moreover, microinjections of IL-6 into the CeA could slightly reduce food intake in vivo in overnight fasted rats. In conclusion, IL-6 containing cells in the CeA express GLP-1R, are close to GLP-1-containing synapses, and demonstrate increased IL-6 mRNA in response to GLP-1R agonist treatment. IL-6, in turn, exerts biological effects in the CeA, possibly via IL-6Rα present in this nucleus.

Original languageEnglish
Article numbere12722
JournalJournal of Neuroendocrinology
Volume31
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

Fingerprint

Interleukin-6
Glucagon-Like Peptide 1
Glucagon-Like Peptide-1 Receptor
Central Amygdaloid Nucleus
Motivation
Staining and Labeling
Food
Messenger RNA
Synaptophysin
Hunger
Electrophysiology
Interleukins
Microinjections
Synapses
Eating
Brain

Keywords

  • amygdala
  • GLP-1
  • immunohistochemistry
  • interleukin-6
  • obesity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Anesten, F., Dalmau Gasull, A., Richard, J. E., Farkas, I., Mishra, D., Taing, L., ... Jansson, J. O. (2019). Interleukin-6 in the central amygdala is bioactive and co-localised with glucagon-like peptide-1 receptor. Journal of Neuroendocrinology, 31(6), [e12722]. https://doi.org/10.1111/jne.12722

Interleukin-6 in the central amygdala is bioactive and co-localised with glucagon-like peptide-1 receptor. / Anesten, Fredrik; Dalmau Gasull, Adrià; Richard, Jennifer E.; Farkas, Imre; Mishra, Devesh; Taing, Lilly; Zhang, Fuping; Poutanen, Matti; Palsdottir, Vilborg; Liposits, Z.; Skibicka, Karolina P.; Jansson, John Olov.

In: Journal of Neuroendocrinology, Vol. 31, No. 6, e12722, 01.06.2019.

Research output: Contribution to journalArticle

Anesten, F, Dalmau Gasull, A, Richard, JE, Farkas, I, Mishra, D, Taing, L, Zhang, F, Poutanen, M, Palsdottir, V, Liposits, Z, Skibicka, KP & Jansson, JO 2019, 'Interleukin-6 in the central amygdala is bioactive and co-localised with glucagon-like peptide-1 receptor', Journal of Neuroendocrinology, vol. 31, no. 6, e12722. https://doi.org/10.1111/jne.12722
Anesten, Fredrik ; Dalmau Gasull, Adrià ; Richard, Jennifer E. ; Farkas, Imre ; Mishra, Devesh ; Taing, Lilly ; Zhang, Fuping ; Poutanen, Matti ; Palsdottir, Vilborg ; Liposits, Z. ; Skibicka, Karolina P. ; Jansson, John Olov. / Interleukin-6 in the central amygdala is bioactive and co-localised with glucagon-like peptide-1 receptor. In: Journal of Neuroendocrinology. 2019 ; Vol. 31, No. 6.
@article{b7437831853d46ae94d8dc0a91b84de0,
title = "Interleukin-6 in the central amygdala is bioactive and co-localised with glucagon-like peptide-1 receptor",
abstract = "Neuronal circuits involving the central amygdala (CeA) are gaining prominence as important centres for regulation of metabolic functions. As a part of the subcortical food motivation circuitry, CeA is associated with food motivation and hunger. We have previously shown that interleukin (IL)-6 can act as a downstream mediator of the metabolic effects of glucagon-like peptide-1 (GLP-1) receptor (R) stimulation in the brain, although the sites of these effects are largely unknown. In the present study, we used the newly generated and validated RedIL6 reporter mouse strain to investigate the presence of IL-6 in the CeA, as well as possible interactions between IL-6 and GLP-1 in this nucleus. IL-6 was present in the CeA, mostly in cells in the medial and lateral parts of this structure, and a majority of IL-6-containing cells also co-expressed GLP-1R. Triple staining showed GLP-1 containing fibres co-staining with synaptophysin close to or overlapping with IL-6 containing cells. GLP-1R stimulation enhanced IL-6 mRNA levels. IL-6 receptor-alpha (IL-6Rα) was found to a large part in neuronal CeA cells. Using electrophysiology, we determined that cells with neuronal properties in the CeA could be rapidly stimulated by IL-6 administration in vitro. Moreover, microinjections of IL-6 into the CeA could slightly reduce food intake in vivo in overnight fasted rats. In conclusion, IL-6 containing cells in the CeA express GLP-1R, are close to GLP-1-containing synapses, and demonstrate increased IL-6 mRNA in response to GLP-1R agonist treatment. IL-6, in turn, exerts biological effects in the CeA, possibly via IL-6Rα present in this nucleus.",
keywords = "amygdala, GLP-1, immunohistochemistry, interleukin-6, obesity",
author = "Fredrik Anesten and {Dalmau Gasull}, Adri{\`a} and Richard, {Jennifer E.} and Imre Farkas and Devesh Mishra and Lilly Taing and Fuping Zhang and Matti Poutanen and Vilborg Palsdottir and Z. Liposits and Skibicka, {Karolina P.} and Jansson, {John Olov}",
year = "2019",
month = "6",
day = "1",
doi = "10.1111/jne.12722",
language = "English",
volume = "31",
journal = "Journal of Neuroendocrinology",
issn = "0953-8194",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Interleukin-6 in the central amygdala is bioactive and co-localised with glucagon-like peptide-1 receptor

AU - Anesten, Fredrik

AU - Dalmau Gasull, Adrià

AU - Richard, Jennifer E.

AU - Farkas, Imre

AU - Mishra, Devesh

AU - Taing, Lilly

AU - Zhang, Fuping

AU - Poutanen, Matti

AU - Palsdottir, Vilborg

AU - Liposits, Z.

AU - Skibicka, Karolina P.

AU - Jansson, John Olov

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Neuronal circuits involving the central amygdala (CeA) are gaining prominence as important centres for regulation of metabolic functions. As a part of the subcortical food motivation circuitry, CeA is associated with food motivation and hunger. We have previously shown that interleukin (IL)-6 can act as a downstream mediator of the metabolic effects of glucagon-like peptide-1 (GLP-1) receptor (R) stimulation in the brain, although the sites of these effects are largely unknown. In the present study, we used the newly generated and validated RedIL6 reporter mouse strain to investigate the presence of IL-6 in the CeA, as well as possible interactions between IL-6 and GLP-1 in this nucleus. IL-6 was present in the CeA, mostly in cells in the medial and lateral parts of this structure, and a majority of IL-6-containing cells also co-expressed GLP-1R. Triple staining showed GLP-1 containing fibres co-staining with synaptophysin close to or overlapping with IL-6 containing cells. GLP-1R stimulation enhanced IL-6 mRNA levels. IL-6 receptor-alpha (IL-6Rα) was found to a large part in neuronal CeA cells. Using electrophysiology, we determined that cells with neuronal properties in the CeA could be rapidly stimulated by IL-6 administration in vitro. Moreover, microinjections of IL-6 into the CeA could slightly reduce food intake in vivo in overnight fasted rats. In conclusion, IL-6 containing cells in the CeA express GLP-1R, are close to GLP-1-containing synapses, and demonstrate increased IL-6 mRNA in response to GLP-1R agonist treatment. IL-6, in turn, exerts biological effects in the CeA, possibly via IL-6Rα present in this nucleus.

AB - Neuronal circuits involving the central amygdala (CeA) are gaining prominence as important centres for regulation of metabolic functions. As a part of the subcortical food motivation circuitry, CeA is associated with food motivation and hunger. We have previously shown that interleukin (IL)-6 can act as a downstream mediator of the metabolic effects of glucagon-like peptide-1 (GLP-1) receptor (R) stimulation in the brain, although the sites of these effects are largely unknown. In the present study, we used the newly generated and validated RedIL6 reporter mouse strain to investigate the presence of IL-6 in the CeA, as well as possible interactions between IL-6 and GLP-1 in this nucleus. IL-6 was present in the CeA, mostly in cells in the medial and lateral parts of this structure, and a majority of IL-6-containing cells also co-expressed GLP-1R. Triple staining showed GLP-1 containing fibres co-staining with synaptophysin close to or overlapping with IL-6 containing cells. GLP-1R stimulation enhanced IL-6 mRNA levels. IL-6 receptor-alpha (IL-6Rα) was found to a large part in neuronal CeA cells. Using electrophysiology, we determined that cells with neuronal properties in the CeA could be rapidly stimulated by IL-6 administration in vitro. Moreover, microinjections of IL-6 into the CeA could slightly reduce food intake in vivo in overnight fasted rats. In conclusion, IL-6 containing cells in the CeA express GLP-1R, are close to GLP-1-containing synapses, and demonstrate increased IL-6 mRNA in response to GLP-1R agonist treatment. IL-6, in turn, exerts biological effects in the CeA, possibly via IL-6Rα present in this nucleus.

KW - amygdala

KW - GLP-1

KW - immunohistochemistry

KW - interleukin-6

KW - obesity

UR - http://www.scopus.com/inward/record.url?scp=85066882341&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066882341&partnerID=8YFLogxK

U2 - 10.1111/jne.12722

DO - 10.1111/jne.12722

M3 - Article

C2 - 31033078

AN - SCOPUS:85066882341

VL - 31

JO - Journal of Neuroendocrinology

JF - Journal of Neuroendocrinology

SN - 0953-8194

IS - 6

M1 - e12722

ER -