| First Author | Zhang T | Year | 2022 |
| Journal | Cell | Volume | 185 |
| Issue | 14 | Pages | 2478-2494.e28 |
| PubMed ID | 35662413 | Mgi Jnum | J:344019 |
| Mgi Id | MGI:7311463 | Doi | 10.1016/j.cell.2022.05.007 |
| Citation | Zhang T, et al. (2022) An inter-organ neural circuit for appetite suppression. Cell 185(14):2478-2494.e28 |
| abstractText | 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. |
