A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila

Takashi Koyama, Selim Terhzaz, Muhammad T. Naseem, Stanislav Nagy, Kim Rewitz, Julian A. T. Dow, Shireen A. Davies and Kenneth V. Halberg ()
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Takashi Koyama: University of Copenhagen
Selim Terhzaz: University of Glasgow
Muhammad T. Naseem: University of Copenhagen
Stanislav Nagy: University of Copenhagen
Kim Rewitz: University of Copenhagen
Julian A. T. Dow: University of Glasgow
Shireen A. Davies: University of Glasgow
Kenneth V. Halberg: University of Copenhagen

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-25445-2

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