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An inter-organ neural circuit for appetite suppression
Open accessAbstract
Glucagon-like peptide-1 (GLP-1) is a signal peptide released from enteroendocrine cells of the lower intestine. GLP-1 exerts anorectic and antimotility actions that protect the body against nutrient malabsorption. However, little is known about how intestinal GLP-1 affects distant organs despite rapid enzymatic inactivation. We show that intestinal GLP-1 inhibits gastric emptying and eating via intestinofugal neurons, a subclass of myenteric neurons that project to abdominal sympathetic ganglia. Remarkably, cell-specific ablation of intestinofugal neurons eliminated intestinal GLP-1 effects, and their chemical activation functioned as a GLP-1 mimetic. GLP-1 sensing by intestinofugal neurons then engaged a sympatho-gastro-spinal-reticular-hypothalamic pathway that links abnormal stomach distension to craniofacial programs for food rejection. Within this pathway, cell-specific activation of discrete neuronal populations caused systemic GLP-1-like effects. These molecularly identified, delimited enteric circuits may be targeted to ameliorate the abdominal bloating and loss of appetite typical of gastric motility disorders.
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“And GLP-1’s action in the brain reduces appetite and may influence energy expenditure.176,210,211”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [176]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“GLP-1 initiates signaling by binding to its receptor, GLP-1R, which is a G-protein-coupled receptor.176,177”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [176]
Experimental — accuracy not yet measuredIn the citing paper
“Interestingly, rather than acting via the canonical mechanosensory VAN pathway (23), ileal GLP-1-evoked gastric distension suppressed eating via a spinal afferent pathway to the parasubthalamic nucleus and a brainstem premotor circuit controlling orofacial food rejection behavior.”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [44]
In the citing paper
“This intestinofugal pathway connects GLP-1R-expressing enteric neurons to stomach-innervating sympathetic neurons which inhibit gastric emptying and eating by a potent nitric oxide neuron-mediated increase in gastric distension.”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [44]
In the citing paper
“A recent study by Zhang et al (44) elegantly delineated the neural circuit basis for this ileal brake, mapping a GLP-1-dependent inter-organ circuit from ileal L-cells to the brain.”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [44]
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Metadata
- Authors
- Zhang, T., Perkins, M. H., Chang, H., Han, W., & de Araujo, I. E.
- Affiliations
- Jinan University (CN)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Han, Wenfei
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 185
- Issue
- 14
- Pages
- 2478-2494.e28
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC9433108
- OpenAlex
- W4281724694
- Cited by
- 192
- References
- 88
- Citations by year
- 2026: 42 · 2025: 53 · 2024: 45 · 2023: 36 · 2022: 16
- FWCI
- 33.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 371 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P20NS123220)
- National Center for Complementary and Integrative Health (R01AT011697)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- glucagon-like peptide-1, appetite suppression, myenteric neurons, enteric nervous system, gastric emptying, hypothalamic pathways, food refusal, bloating, gastric motility disorders
- MeSH terms
- Abdomen, Glucagon-Like Peptide-1 Receptor, Animals, Appetite, Cell Communication, Ileum, Male, Neurons, Nitric Oxide, Stomach, Signal Transduction, Mice, Glucagon-Like Peptide 1
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