A gut-derived hormone suppresses sugar appetite and regulates food choice in Drosophila

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Animals must adapt their dietary choices to meet their nutritional needs. How these needs are detected and translated into nutrient-specific appetites that drive food-choice behaviours is poorly understood. Here we show that enteroendocrine cells of the adult female Drosophila midgut sense nutrients and in response release neuropeptide F (NPF), which is an ortholog of mammalian neuropeptide Y-family gut-brain hormones. Gut-derived NPF acts on glucagon-like adipokinetic hormone (AKH) signalling to induce sugar satiety and increase consumption of protein-rich food, and on adipose tissue to promote storage of ingested nutrients. Suppression of NPF-mediated gut signalling leads to overconsumption of dietary sugar while simultaneously decreasing intake of protein-rich yeast. Furthermore, gut-derived NPF has a female-specific function in promoting consumption of protein-containing food in mated females. Together, our findings suggest that gut NPF-to-AKH signalling modulates specific appetites and regulates food choice to ensure homeostatic consumption of nutrients, providing insight into the hormonal mechanisms that underlie nutrient-specific hungers.

TidsskriftNature Metabolism
Udgave nummer11
Sider (fra-til)1532-1550
Antal sider19
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Anti-Akh was a kind gift from J. Park (University of Tennessee). Anti-AstC was a generous gift from J. Veenstra (University of Bordeaux) and M. Zandawala (Brown University). R57C10-GAL80 was kindly given by R. Niwa (University of Tsukuba). AKH mutant and NPFR::2A::GAL4 flies were kindly provided by S. Kondo (Tokyo University of Science). UAS-TrpA1[attP2] was kindly given by C. Wegener (University of Würzburg). voilà-GAL4 (ref.57) was kindly given by A. Scopelliti (University of Glasgow). Df(3L)delta130 (SP deletion) was a kind gift from A. von Philipsborn (Aarhus University). UAS-LexA::VP16::NFAT; LexAop-luciferase was a kind gift from M. Rosbash (Brandeis University). We thank the Vienna Drosophila Resource Center and the University of Indiana Bloomington Drosophila Stock Center for fly lines, and we also thank the University of Iowa Developmental Studies Hybridoma bank for providing anti-Prospero. This work was supported by Novo Nordisk Foundation grant no. NNF19OC0054632 and Lundbeck Foundation grant no. 2019-772 to K.R. T.K. and K.V.H. were supported by funding from the Villum Foundation (grant no. 15365) and Danish Council for Independent Research Natural Sciences (grant no. 9064-00009B) to K.V.H. The Zeiss LSM 900 confocal microscope was purchased with a generous grant from the Carlsberg Foundation (grant no. CF19-0353).

Publisher Copyright:
© 2022, The Author(s).

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