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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

Journal article
Authors Fredrik Anesten
Devesh Mishra
Adria Dalmau Gasull
Linda Engström-Ruud
Jakob Bellman
Vilborg Palsdottir
F Zhang
S. Trapp
Karolina P Skibicka
Matti Poutanen
John-Olov Jansson
Published in Neuroendocrinology
Volume 109
Issue 4
Pages 310-321
ISSN 0028-3835
Publication year 2019
Published at Wallenberg Laboratory
Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Physiology
Pages 310-321
Language en
Links dx.doi.org/10.1159/000499693
Keywords Hindbrain, RedIL6, Immunohistochemistry, In situ hybridization, Interleukins, gene knockout, cgrp neurons, body-weight, food-intake, il-6, cancer, alpha, mice, hindbrain, energy, Endocrinology & Metabolism, Neurosciences & Neurology
Subject categories Neurosciences

Abstract

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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