PROJECT SUMMARY/ABSTRACT The long-term goal of this project is to uncover how the gut-brain axis regulates appetite in a nutrient-specific manner. In mammals, enteroendocrine cells in the gastrointestinal tract release a repertoire neuropeptides to regulate food intake. However, it is not clear how nutrients are represented by gut neuropeptides. The research outlined here takes advantage of the anatomical simplicity and the powerful genetic toolkit of the Drosophila to address the questions of how macronutrients — carbohydrates, amino acids and fatty acids — are transformed into a neuropeptide code and how nutritional information is processed to regulate appetite. The proposed study focuses on gut neuropeptide — what macronutrients they represent (Aim 1) and whether they are anorexigenic hormones (Aim 2). In Aim 3, we will test the hypothesis that the level of an anorexigenic hormone represents not only the quantity but also the quality of amino acids. Results from these studies are expected to establish a neuropeptide code for macronutrients providing mechanistic insights into how food intake is regulated in a nutrient-specific manner. These insights are highly relevant to human health as reducing food intake by designed diets could provide a new avenue to fight the obesity epidemic