Cellular and Molecular basis of protein-specific appetite

For survival and fitness, animals must regulate not only the amount, but also the type of food to consume. Indeed, hunger is not a unitary phenomenon, but rather can exist for specific nutrients. Protein is an indispensable macronutrient, particularly important during anabolic states such as pregnancy and infancy, yet the mechanisms underlying protein-specific appetite remain unclear. We identified a small subset of dopaminergic neurons (DA-WED) that encodes protein-specific hunger in Drosophila. Functional imaging and electrophysiological experiments revealed that the activity of DA-WED neurons correlates with the protein need. In response to substantial protein starvation, these neurons simultaneously increased protein intake and suppressed sucrose consumption, by signaling to distinct cellular targets via different dopamine receptors. Using these findings as entry point, we continued to investigate the molecular mechanisms regulating the homeostatic protein feeding. Our preliminary data suggest that a series of metabolic changes occur following protein starvation, some of which may be detected by the protein hunger circuit to signal protein scarcity. Our results thus uncover crucial circuit and molecular mechanisms by which animals adjust their dietary strategy to maintain protein homeostasis.