Chronic dysfunction of Stromal interaction molecule by pulsed RNAi induction in fat tissue impairs organismal energy homeostasis in Drosophila.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
06 05 2019
Historique:
received: 10 07 2018
accepted: 15 04 2019
entrez: 8 5 2019
pubmed: 8 5 2019
medline: 15 9 2020
Statut: epublish

Résumé

Obesity is a progressive, chronic disease, which can be caused by long-term miscommunication between organs. It remains challenging to understand how chronic dysfunction in a particular tissue remotely impairs other organs to eventually imbalance organismal energy homeostasis. Here we introduce RNAi Pulse Induction (RiPI) mediated by short hairpin RNA (shRiPI) or double-stranded RNA (dsRiPI) to generate chronic, organ-specific gene knockdown in the adult Drosophila fat tissue. We show that organ-restricted RiPI targeting Stromal interaction molecule (Stim), an essential factor of store-operated calcium entry (SOCE), results in progressive fat accumulation in fly adipose tissue. Chronic SOCE-dependent adipose tissue dysfunction manifests in considerable changes of the fat cell transcriptome profile, and in resistance to the glucagon-like Adipokinetic hormone (Akh) signaling. Remotely, the adipose tissue dysfunction promotes hyperphagia likely via increased secretion of Akh from the neuroendocrine system. Collectively, our study presents a novel in vivo paradigm in the fly, which is widely applicable to model and functionally analyze inter-organ communication processes in chronic diseases.

Identifiants

pubmed: 31061470
doi: 10.1038/s41598-019-43327-y
pii: 10.1038/s41598-019-43327-y
pmc: PMC6502815
doi:

Substances chimiques

Aralar protein, Drosophila 0
Calcium-Binding Proteins 0
Drosophila Proteins 0
Insect Hormones 0
Isoenzymes 0
Oligopeptides 0
RNA, Small Interfering 0
Stim protein, Drosophila 0
Stromal Interaction Molecule 1 0
DAKH peptide 129204-82-6
Malate Dehydrogenase EC 1.1.1.37
Aspartate Aminotransferase, Cytoplasmic EC 2.6.1.-
Calcium SY7Q814VUP
Pyrrolidonecarboxylic Acid SZB83O1W42

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6989

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Auteurs

Yanjun Xu (Y)

Max-Planck-Institut für biophysikalische Chemie, Research Group Molecular Physiology, Am Faβberg 11, D-37077, Göttingen, Germany. yanjun.xu@helmholtz-muenchen.de.
Max-Planck-Institut für biophysikalische Chemie, Department of Molecular Developmental Biology, Am Faβberg 11, D-37077, Göttingen, Germany. yanjun.xu@helmholtz-muenchen.de.
Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, D-85764, Neuherberg, München, Germany. yanjun.xu@helmholtz-muenchen.de.

Annika F Borcherding (AF)

Max-Planck-Institut für biophysikalische Chemie, Research Group Molecular Physiology, Am Faβberg 11, D-37077, Göttingen, Germany.

Christoph Heier (C)

University of Graz, Institute of Molecular Biosciences, Humboldtstrasse 50/2.OG, A-8010, Graz, Austria.

Gu Tian (G)

Christian-Albrechts University Kiel, Zoology, Molecular Physiology, 24098, Kiel, Germany.
Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Kiel, Germany.

Thomas Roeder (T)

Christian-Albrechts University Kiel, Zoology, Molecular Physiology, 24098, Kiel, Germany.
Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Kiel, Germany.

Ronald P Kühnlein (RP)

Max-Planck-Institut für biophysikalische Chemie, Research Group Molecular Physiology, Am Faβberg 11, D-37077, Göttingen, Germany. ronald.kuehnlein@uni-graz.at.
University of Graz, Institute of Molecular Biosciences, Humboldtstrasse 50/2.OG, A-8010, Graz, Austria. ronald.kuehnlein@uni-graz.at.
BioTechMed Graz, Graz, Austria. ronald.kuehnlein@uni-graz.at.

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Classifications MeSH