marmitedefines a novel conserved neuropeptide family mediating nutritional homeostasis

Neuropeptides play a key role in regulating physiology and behavior, including feeding. While animals modify their food choices to respond to the lack of specific nutrients, the mechanisms mediating nutrient-specific appetites remain unclear. Here, we identifiedmarmite(mmt), a previously uncharacterizedDrosophila melanogastergene encoding a secreted peptide that controls feeding decisions. We show that bothmmtmutants and neuronal knockdown ofmmtspecifically increased the intake of proteinaceous food, whereas neuronalmmtoverexpression reduced protein appetite.mmtexpression is also higher in animals maintained on amino acid rich food, suggesting thatmmtencodes a protein-specific satiety signal. Mmt is expressed in a small number of neurons in the adult nervous system, with a single pair of neurons modulating protein appetite. Finally, sequence and phylogenetic analysis showed thatmmtis part of an ancient and conserved family of neuropeptides, including the poorly understood vertebrateneuropeptides BandWgenes. Functional experiments showed thatmmtand vertebrateNPBandNPWmodulate food intake in both flies and mice. Therefore, we discovered an ancient family of neuropeptides involved in controlling feeding across phyla.