An inter-organ neural circuit for appetite suppression

Cell. 2022 Jul 7;185(14):2478-2494.e28. doi: 10.1016/j.cell.2022.05.007. Epub 2022 Jun 2.


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.

Keywords: Appetite suppression; GLP-1; enteric neurons; gut peptides; gut-brain axis; interoception.

Publication types

  • Video-Audio Media

MeSH terms

  • Abdomen
  • Animals
  • Appetite*
  • Cell Communication
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Ileum* / innervation
  • Ileum* / metabolism
  • Male
  • Mice
  • Neurons* / metabolism
  • Nitric Oxide / metabolism
  • Signal Transduction
  • Stomach* / innervation
  • Stomach* / metabolism


  • Glucagon-Like Peptide-1 Receptor
  • Nitric Oxide
  • Glucagon-Like Peptide 1