TY - JOUR
T1 - Glucagon-Like Peptide-1-, but not Growth and Differentiation Factor 15-, Receptor Activation Increases the Number of Interleukin-6-Expressing Cells in the External Lateral Parabrachial Nucleus
AU - Anesten, Fredrik
AU - Mishra, Devesh
AU - Dalmau Gasull, Adrià
AU - Engström-Ruud, Linda
AU - Bellman, Jakob
AU - Palsdottir, Vilborg
AU - Zhang, Fuping
AU - Trapp, Stefan
AU - Skibicka, Karolina P.
AU - Poutanen, Matti
AU - Jansson, John Olov
N1 - Funding Information:
We thank Erik Schéle for the schematic illustration of the key findings of the paper. We thank the Centre for Cellular Imaging at the University of Gothenburg and the National Microscopy Infrastructure, NMI (VR-RFI 2016-00968) for the use of imaging equipment, as well as support received from Julia Fernandez-Rodriguez, Maria Smedh, and Carolina Tängemo. We also thank the personnel at Turku Center for Disease Modeling (www. tcdm.fi) for skillful technical assistance in generating the reporter mouse line for IL-6. This work was supported by the Novo-Nordisk Foundation, the Swedish Research Council, the Swedish Government (under the Avtal om Läkarutbildning och Medi-cinsk Forskning [Agreement for Medical Education and Research]), the Knut and Alice Wallenberg Foundation, EC Frame-work 7, and the Torsten Söderbergs Foundation (to J.-O.J.) and by the Swedish Research Council (2014-2945 to K.P.S.), Wallen-berg Foundation (to K.P.S.), Novo Nordisk Foundation Excellence project grant (to KPS), and Ragnar Söderberg Foundation (K.P.S.). Medical Research Council (MRC) grant MR/N02589X/1 (to S.T.).
Funding Information:
We thank Erik Schéle for the schematic illustration of the key findings of the paper. We thank the Centre for Cellular Imaging at the University of Gothenburg and the National Microscopy Infrastructure, NMI (VR-RFI 2016-00968) for the use of imaging equipment, as well as support received from Julia Fernandez-Rodriguez, Maria Smedh, and Carolina Tängemo. We also thank the personnel at Turku Center for Disease Modeling (www.tcdm.fi) for skillful technical assistance in generating the reporter mouse line for IL-6. This work was supported by the NovoNordisk Foundation, the Swedish Research Council, the Swedish Government (under the Avtal om Läkarutbildning och Medicinsk Forskning [Agreement for Medical Education and Research]), the Knut and Alice Wallenberg Foundation, EC Framework 7, and the Torsten Söderbergs Foundation (to J.-O.J.) and by the Swedish Research Council (2014-2945 to K.P.S.), Wallenberg Foundation (to K.P.S.), Novo Nordisk Foundation Excellence project grant (to KPS), and Ragnar Söderberg Foundation (K.P.S.). Medical Research Council (MRC) grant MR/N02589X/1 (to S.T.).
Publisher Copyright:
© 2019 S. Karger AG, Basel.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Interleukin (IL)-6 in the hypothalamus and hindbrain is an important downstream mediator of suppression of body weight and food intake by glucagon-like peptide-1 (GLP-1) receptor stimulation. CNS GLP-1 is produced almost exclusively in prepro-glucagon neurons in the nucleus of the solitary tract. These neurons innervate energy balance-regulating areas, such as the external lateral parabrachial nucleus (PBNel); essential for induction of anorexia. Using a validated novel IL-6-reporter mouse strain, we investigated the interactions in PBNel between GLP-1, IL-6, and calcitonin gene-related peptide (CGRP, a well-known mediator of anorexia). We show that PBNel GLP-1R-containing cells highly (to about 80%) overlap with IL-6-containing cells on both protein and mRNA level. Intraperitoneal administration of a GLP-1 analogue exendin-4 to mice increased the proportion of IL-6-containing cells in PBNel 3-fold, while there was no effect in the rest of the lateral parabrachial nucleus. In contrast, injections of an anorexigenic peptide growth and differentiation factor 15 (GDF15) markedly increased the proportion of CGRP-containing cells, while IL-6-containing cells were not affected. In summary, GLP-1R are found on IL-6-producing cells in PBNel, and GLP-1R stimulation leads to an increase in the proportion of cells with IL-6-reporter fluorescence, supporting IL-6 mediation of GLP-1 effects on energy balance.
AB - Interleukin (IL)-6 in the hypothalamus and hindbrain is an important downstream mediator of suppression of body weight and food intake by glucagon-like peptide-1 (GLP-1) receptor stimulation. CNS GLP-1 is produced almost exclusively in prepro-glucagon neurons in the nucleus of the solitary tract. These neurons innervate energy balance-regulating areas, such as the external lateral parabrachial nucleus (PBNel); essential for induction of anorexia. Using a validated novel IL-6-reporter mouse strain, we investigated the interactions in PBNel between GLP-1, IL-6, and calcitonin gene-related peptide (CGRP, a well-known mediator of anorexia). We show that PBNel GLP-1R-containing cells highly (to about 80%) overlap with IL-6-containing cells on both protein and mRNA level. Intraperitoneal administration of a GLP-1 analogue exendin-4 to mice increased the proportion of IL-6-containing cells in PBNel 3-fold, while there was no effect in the rest of the lateral parabrachial nucleus. In contrast, injections of an anorexigenic peptide growth and differentiation factor 15 (GDF15) markedly increased the proportion of CGRP-containing cells, while IL-6-containing cells were not affected. In summary, GLP-1R are found on IL-6-producing cells in PBNel, and GLP-1R stimulation leads to an increase in the proportion of cells with IL-6-reporter fluorescence, supporting IL-6 mediation of GLP-1 effects on energy balance.
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U2 - 10.1159/000499693
DO - 10.1159/000499693
M3 - Article
C2 - 30889580
AN - SCOPUS:85066910455
SN - 0028-3835
VL - 109
SP - 310
EP - 321
JO - Neuroendocrinology
JF - Neuroendocrinology
IS - 4
ER -
