An inter-organ neural circuit for appetite suppression

Zhang, T; Perkins, MH; Chang, H; Han, W; de Araujo, IE

doi:10.1016/j.cell.2022.05.007

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An inter-organ neural circuit for appetite suppression

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https://www.sciencedirect.com/science/article/abs/pii/S0092867422005918
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Zhang, T., Perkins, M., Chang, H., Han, W., & de Araujo, I. (2023). An inter-organ neural circuit for appetite suppression. Talk presented at Neurometabolism in health and disease in partnership with A*STAR's Institute of Molecular and Cell Biology (IMCB). Singapore. 2023-04-26 - 2023-04-28.

Cite as: https://hdl.handle.net/21.11116/0000-000D-524C-2

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.