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Central and peripheral GLP-1 systems independently suppress eating
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Brierley, Daniel I., Holt, Marie K., Singh, Arashdeep, de Araujo, Alan, McDougle, Molly, Vergara, Macarena, Afaghani, Majd H., Lee, Shin Jae, Scott, Karen, Maske, Calyn, Langhans, Wolfgang, Krause, Eric, de Kloet, Annette, Gribble, Fiona M., Reimann, Frank, Rinaman, Linda, de Lartigue, Guillaume and Trapp, Stefan (2021) Central and peripheral GLP-1 systems independently suppress eating. Nature Metabolism, 3 (2). pp. 258-273. doi:10.1038/s42255-021-00344-4 ISSN 2522-5812.
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Official URL: http://doi.org/10.1038/s42255-021-00344-4
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. 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 PPGNTS neurons encode satiation in mice, consistent with vagal signalling of gastrointestinal distension. However, PPGNTS neurons predominantly receive vagal input from oxytocin-receptor-expressing vagal neurons, rather than those expressing GLP-1 receptors. PPGNTS neurons are not necessary for eating suppression by GLP-1 receptor agonists, and concurrent PPGNTS 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 PPGNTS neurons in combination with GLP-1 receptor agonists as an obesity treatment strategy.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
Journal or Publication Title: | Nature Metabolism | ||||||
Publisher: | Springer Nature | ||||||
ISSN: | 2522-5812 | ||||||
Official Date: | February 2021 | ||||||
Dates: |
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Volume: | 3 | ||||||
Number: | 2 | ||||||
Page Range: | pp. 258-273 | ||||||
DOI: | 10.1038/s42255-021-00344-4 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Restricted or Subscription Access |
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