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

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 cent...

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Autores principales: Koyama, Takashi, Terhzaz, Selim, Naseem, Muhammad T., Nagy, Stanislav, Rewitz, Kim, Dow, Julian A. T., Davies, Shireen A., Halberg, Kenneth V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405823/
https://www.ncbi.nlm.nih.gov/pubmed/34462441
http://dx.doi.org/10.1038/s41467-021-25445-2
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author Koyama, Takashi
Terhzaz, Selim
Naseem, Muhammad T.
Nagy, Stanislav
Rewitz, Kim
Dow, Julian A. T.
Davies, Shireen A.
Halberg, Kenneth V.
author_facet Koyama, Takashi
Terhzaz, Selim
Naseem, Muhammad T.
Nagy, Stanislav
Rewitz, Kim
Dow, Julian A. T.
Davies, Shireen A.
Halberg, Kenneth V.
author_sort Koyama, Takashi
collection PubMed
description 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.
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spelling pubmed-84058232021-09-22 A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila Koyama, Takashi Terhzaz, Selim Naseem, Muhammad T. Nagy, Stanislav Rewitz, Kim Dow, Julian A. T. Davies, Shireen A. Halberg, Kenneth V. Nat Commun Article 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. Nature Publishing Group UK 2021-08-30 /pmc/articles/PMC8405823/ /pubmed/34462441 http://dx.doi.org/10.1038/s41467-021-25445-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Koyama, Takashi
Terhzaz, Selim
Naseem, Muhammad T.
Nagy, Stanislav
Rewitz, Kim
Dow, Julian A. T.
Davies, Shireen A.
Halberg, Kenneth V.
A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila
title A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila
title_full A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila
title_fullStr A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila
title_full_unstemmed A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila
title_short A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila
title_sort nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult drosophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405823/
https://www.ncbi.nlm.nih.gov/pubmed/34462441
http://dx.doi.org/10.1038/s41467-021-25445-2
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