An inter-organ neural circuit for appetite suppression.
Cell
; 185(14): 2478-2494.e28, 2022 07 07.
Article
em En
| MEDLINE
| ID: mdl-35662413
ABSTRACT
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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Base de dados:
MEDLINE
Assunto principal:
Apetite
/
Estômago
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Peptídeo 1 Semelhante ao Glucagon
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Íleo
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Neurônios
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article