Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.03.234427v1?rss=1 Authors: Brierley, D. I., Holt, M. K., Singh, A., de Araujo, A., Vergana, M., Afaghani, M., Lee, S. J., Scott, K., Langhans, W., Krause, E., de Kloet, A., Gribble, F., Reimann, F., Rinaman, L., De Lartigue, G., Trapp, S. Abstract: The anorexigenic peptide glucagon-like peptide-1 (GLP-1) is secreted from gut enteroendocrine cells and brain preproglucagon (PPG) neurons, which respectively define the peripheral and central GLP-1 systems. As peripheral satiation signals are integrated in the nucleus tractus solitarius (NTS), PPGNTS neurons are assumed to link the peripheral and central GLP-1 systems, forming a unified GLP-1 gut-brain satiation circuit. This hypothesis, however, remains unsubstantiated. We report that PPGNTS neurons encode satiation in mice, consistent with vagal gastrointestinal distension signalling. However, PPGNTS neurons predominantly receive vagal input from oxytocin receptor-expressing vagal neurons, rather than those expressing GLP-1 receptors. Furthermore, PPGNTS neurons are not necessary for eating suppression induced by the GLP-1 receptor agonists liraglutide or semaglutide, and semaglutide and PPGNTS neuron activation additively suppress eating. Central and peripheral GLP-1 systems thus suppress eating via independent gut-brain circuits, hence PPGNTS neurons represent a rational pharmacological target for anti-obesity combination therapy with GLP-1 receptor agonists. Copy rights belong to original authors. Visit the link for more info