A neuronal relay mediates a nutrient responsive gut/fat body axis regulating energy homeostasis in adult Drosophila

Scopelliti, A., Bauer, C. , Yu, Y., Zhang, T., Kruspig, B., Murphy, D. J. , Vidal, M., Maddocks, O. D.K. and Cordero, J. B. (2019) A neuronal relay mediates a nutrient responsive gut/fat body axis regulating energy homeostasis in adult Drosophila. Cell Metabolism, 29(2), 269-284.e10. (doi: 10.1016/j.cmet.2018.09.021) (PMID:30344016) (PMCID:PMC6370946)

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The control of systemic metabolic homeostasis involves complex inter-tissue programs that coordinate energy production, storage, and consumption, to maintain organismal fitness upon environmental challenges. The mechanisms driving such programs are largely unknown. Here, we show that enteroendocrine cells in the adult Drosophila intestine respond to nutrients by secreting the hormone Bursicon α, which signals via its neuronal receptor DLgr2. Bursicon α/DLgr2 regulate energy metabolism through a neuronal relay leading to the restriction of glucagon-like, adipokinetic hormone (AKH) production by the corpora cardiaca and subsequent modulation of AKH receptor signaling within the adipose tissue. Impaired Bursicon α/DLgr2 signaling leads to exacerbated glucose oxidation and depletion of energy stores with consequent reduced organismal resistance to nutrient restrictive conditions. Altogether, our work reveals an intestinal/neuronal/adipose tissue inter-organ communication network that is essential to restrict the use of energy and that may provide insights into the physiopathology of endocrine-regulated metabolic homeostasis.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Murphy, Professor Daniel and Yu, Dr Yachuan and Vidal, Dr Marcos and Maddocks, Professor Oliver and Cordero, Professor Julia and Zhang, Mr Tong and Bauer, Christin and Kruspig, Dr Bjorn and Scopelliti, Mr Alessandro
Authors: Scopelliti, A., Bauer, C., Yu, Y., Zhang, T., Kruspig, B., Murphy, D. J., Vidal, M., Maddocks, O. D.K., and Cordero, J. B.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cell Metabolism
Publisher:Elsevier (Cell Press)
ISSN (Online):1932-7420
Published Online:18 October 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Cell Metabolism 29(2): 269-284.e10
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
633022Regulation of stem cell function during tissue homeostasis and transformationJulia CorderoWellcome Trust (WELLCOTR)104103/Z/14/ZRI CANCER SCIENCES