A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila
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- A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila
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Animals maintain metabolic homeostasis by modulating the activity of specialized organs that adjust internal metabolism to external conditions. However, the hormonal signals coordinating these functions are incompletely characterized. Here we show that six neurosecretory cells in the Drosophila central nervous system respond to circulating nutrient levels by releasing Capa hormones, homologs of mammalian neuromedin U, which activate the Capa receptor (CapaR) in peripheral tissues to control energy homeostasis. Loss of Capa/CapaR signaling causes intestinal hypomotility and impaired nutrient absorption, which gradually deplete internal nutrient stores and reduce organismal lifespan. Conversely, increased Capa/CapaR activity increases fluid and waste excretion. Furthermore, Capa/CapaR inhibits the release of glucagon-like adipokinetic hormone from the corpora cardiaca, which restricts energy mobilization from adipose tissue to avoid harmful hyperglycemia. Our results suggest that the Capa/CapaR circuit occupies a central node in a homeostatic program that facilitates the digestion and absorption of nutrients and regulates systemic energy balance.
|Udgivet - 2021
We are grateful to Manfred Frasch, Achim Paululat, Diogo Manuel, Jae Park, Jan Veenstra, Dalibor Kodrík, Bloomington Drosophila stock Center, Vienna Drosophila Resource Center and Developmental Studies Hybridoma Bank for the generous sharing of resources, as well as to Michael Texada for giving critical comments to the manuscript. Camilla Trang Vo and Christina Papamichail are thanked for helping with pupal weight and developmental timing quantifications and Manal Merimi is thanked for help with qRT-PCR analysis. This work was supported by funding from the Villum Foundation (15365) and Danish Council for Independent Research Natural Sciences (9064-00009B) to KVH. Additional funding was given by UKRI BBSRC (BB/P008097/ 1) to SD, JATD and ST as well as by Novo Nordisk Foundation (16OC0021270) to KR. ST was additionally funded by United Kingdom Medical Research Council (MC_UU_12014/8).
© 2021, The Author(s).
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