Periphery signals generated by Piezo-mediated stomach stretch and neuromedin-mediated glucose loads regulate the Drosophila brain nutrient sensor

Nutrient sensors allow animals to identify foods rich in specific nutrients. The Drosophila nutrient sensor, DH44 neurons, helps the fly to detect nutritive sugar. This sensor becomes operational during starvation; however, the mechanisms by which DH44 neurons or other nutrient sensors are regulated remain unclear. Here, we identified two satiety signals that inhibit DH44 neurons: 1) Piezo-mediated stomach/crop stretch after food ingestion; 2) Neuromedin/Hugin neurosecretory neurons in the ventral nerve cord (VNC) activated by an increase in the internal glucose levels. A subset of Piezo + neurons that express DH44 neuropeptide project to the crop. We found that DH44 neuronal activity and food intake were stimulated following a knockdown of piezo in DH44 neurons or silencing of Hugin neurons in the VNC, even in fed flies. Together, we propose that these two qualitatively distinct peripheral signals work in concert to regulate the DH44 nutrient sensor during the fed state. Oh et al. identified two-distinct satiety signals that inhibit Drosophila nutrient sensor, DH44 neurons, through the gut-brain axis during fed state. Gastric mechanosensation mediated by Piezo channels in the stomach and peptidergic sugar-sensing Hugin TS neurons in the ventral nerve cord inhibit glucose-induced response of DH44 neurons to suppress sugar overconsumption.