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

Koyama, T., Terhzaz, S. , Naseem, M. T., Nagy, S., Rewitz, K., Dow, J. A.T. , Davies, S. A. and Halberg, K. V. (2021) A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila. Nature Communications, 12, 5178. (doi: 10.1038/s41467-021-25445-2) (PMID:34462441) (PMCID:PMC8405823)

[img] Text
250599.pdf - Published Version
Available under License Creative Commons Attribution.

3MB

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dow, Professor Julian and Terhzaz, Dr Selim and Halberg, Dr Kenneth and Davies, Professor Shireen
Authors: Koyama, T., Terhzaz, S., Naseem, M. T., Nagy, S., Rewitz, K., Dow, J. A.T., Davies, S. A., and Halberg, K. V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Nature Communications 12: 5178
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173817Functional analysis of insect neuropeptide G protein-coupled receptorsShireen DaviesBiotechnology and Biological Sciences Research Council (BBSRC)BB/P008097/1MCSB - Integrative & Systems Biology
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH