Work

Control of feeding behavior by modified retrograde AAV to the gastrointestinal tract nerve afferents

Year: 2025

Type: article

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.

Source: Scientific Reports

DOI: 10.1038/s41598-025-31377-4