Open AccessCentral and peripheral GLP-1 systems independently suppress eating
Author(s) -
Daniel I. Brierley,
Marie K. Holt,
Avninder Singh,
Alan de Araujo,
Molly McDougle,
Macarena Vergara,
Majd H. Afaghani,
Shin-Jae Lee,
Karen A. Scott,
Calyn B. Maske,
Wolfgang Langhans,
Eric G. Krause,
Annette D. de Kloet,
Fiona M. Gribble,
Frank Reimann,
Linda Rinaman,
Guillaume de Lartigue,
Stefan Trapp
Publication year - 2021
Publication title -
nature metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.834
H-Index - 22
ISSN - 2522-5812
DOI - 10.1038/s42255-021-00344-4
Subject(s) - glucagon like peptide 1 , enteroendocrine cell , receptor , peripheral , neuroscience , semaglutide , neuron , endocrinology , medicine , gastric distension , glucagon like peptide 1 receptor , biology , distension , liraglutide , agonist , endocrine system , hormone , diabetes mellitus , type 2 diabetes
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. PPG neurons in the nucleus tractus solitarii (NTS) are widely assumed to link the peripheral and central GLP-1 systems in a unified gut-brain satiation circuit. However, direct evidence for this hypothesis is lacking, and the necessary circuitry remains to be demonstrated. Here we show that PPG NTS neurons encode satiation in mice, consistent with vagal signalling of gastrointestinal distension. However, PPG NTS neurons predominantly receive vagal input from oxytocin-receptor-expressing vagal neurons, rather than those expressing GLP-1 receptors. PPG NTS neurons are not necessary for eating suppression by GLP-1 receptor agonists, and concurrent PPG NTS neuron activation suppresses eating more potently than semaglutide alone. We conclude that central and peripheral GLP-1 systems suppress eating via independent gut-brain circuits, providing a rationale for pharmacological activation of PPG NTS neurons in combination with GLP-1 receptor agonists as an obesity treatment strategy.