Sugar Promotes Feeding in Flies via the Serine Protease Homolog scarface

Summary: A balanced diet of macronutrients is critical for animal health. A lack of specific elements can have profound effects on behavior, reproduction, and lifespan. Here, we used Drosophila to understand how the brain responds to carbohydrate deprivation. We found that serine protease homologs (SPHs) are enriched among genes that are transcriptionally regulated in flies deprived of carbohydrates. Stimulation of neurons expressing one of these SPHs, Scarface (Scaf), or overexpression of scaf positively regulates feeding on nutritious sugars, whereas inhibition of these neurons or knockdown of scaf reduces feeding. This modulation of food intake occurs only in sated flies while hunger-induced feeding is unaffected. Furthermore, scaf expression correlates with the presence of sugar in the food. As Scaf and Scaf neurons promote feeding independent of the hunger state, and the levels of scaf are positively regulated by the presence of sugar, we conclude that scaf mediates the hedonic control of feeding. : Regulation of feeding on nutritious food is critical for survival. Using an unbiased, transcriptional-based approach, Prasad and Hens identify serine protease homologs as neuromodulators in the fly brain. The authors elucidate the role of scarface and neurons labeled by Scarface in promoting feeding on nutritious food without evoking hunger. Keywords: feeding behavior, macronutrient, Scarface, hedonic control, Drosophila, carbohydrate