Control of feeding behavior by modified retrograde AAV to the gastrointestinal tract nerve afferents.
| Publication Type | Academic Article |
| Authors | Marongiu R, Wang J, Unda S, Barbera J, Velazquez L, Li R, Jimenez-Gonzalez M, Tower W, de Silva N, Retik R, Stanley S, Kaplitt M |
| Journal | Sci Rep |
| Volume | 16 |
| Issue | 1 |
| Pagination | 1773 |
| Date Published | 12/14/2025 |
| ISSN | 2045-2322 |
| Keywords | Dependovirus, Feeding Behavior, Gastrointestinal Tract, Neurons, Afferent |
| Abstract | Vagal afferents originating in the upper gastrointestinal (GI) tract convey critical satiety signals but have remained challenging to target with precision. Here, we exploited a modified retrograde AAV2/rh10 vector delivered to the gastric wall to selectively transduce stomach-innervating nodose ganglion neurons and express the excitatory DREADD receptor hM3Dq. Chemogenetic activation of these afferents in mice acutely suppressed food intake by over 50% and induced robust c-Fos expression in neurons of the nucleus tractus solitarius and ventromedial (VMH) and arcuate nuclei of the hypothalamus, while chronic stimulation during high-fat feeding attenuated diet-induced weight gain by nearly 40%. This minimally invasive, organ-targeted gene-delivery strategy affords reversible control over visceral sensory pathways and holds promise as a foundation for novel obesity and metabolic-disorder therapies. |
| DOI | 10.1038/s41598-025-31377-4 |
| PubMed ID | 41392163 |
| PubMed Central ID | PMC12804985 |