The integration of nutrient-specific satiety signals in the brain to control food intake.

PROJECT SUMMARY/ABSTRACT Most studies in the field of feeding regulation have primarily concentrated on the impact of energy homeostasis on feeding behavior, with less attention to the hormones and neural mechanisms governing nutrient-specific feeding. Leveraging the genetic advantages and well-characterized nervous and gut

systems of the fruit fly, Drosophila melanogaster, we aim to explore the neuronal mechanisms that underlie nutrient-specific feeding regulation. Our preliminary findings highlight a specific group of Dh31R+/AstC+ neurons as target neurons for the gut-derived peptide Diuretic hormone 31 (Dh31) in regulating protein

consumption. Additionally, we have identified another subset of gut cells that are responsive to sucrose intake and the essential role of its receptor in suppressing sucrose feeding. This proposal aims to investigate the molecular and neural mechanisms underlying the regulation of dietary protein and sucrose consumption,

with a particular focus on how gut-derived peptide hormones, triggered by specific nutrient intake, activate neural targets in the brain to govern nutrient- specific feeding regulation. Furthermore, we propose identifying the central neural hub where various nutrient- specific feeding circuits converge to modulate food

intake. The proposed experiments include characterizing the neural substrate of the gut hormone Dh31 responsible for suppressing protein feeding (Aim 1), elucidating the satiety signal for sucrose and understanding the neural mechanism governing sucrose feeding regulation (Aim 2), and identifying the

central hub that integrates signals for both protein and sucrose to regulate overall food intake (Aim 3). The expected mechanistic insights from this research will illuminate the processes through which diverse macronutrient signals influence feeding behavior, highlighting the interplay between gut-derived signals and

neural pathways.