GLP-1-, but not GDF-15-, receptor activation increases the number of IL-6-expressing cells in the external lateral parabrachial nucleus

Background/Aims 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. Methods 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. Results 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 PBN. 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. Conclusion 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.