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Sci Rep. 2019 May 6;9(1):6989. doi: 10.1038/s41598-019-43327-y.

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

Author information

1
Max-Planck-Institut für biophysikalische Chemie, Research Group Molecular Physiology, Am Faβberg 11, D-37077, Göttingen, Germany. yanjun.xu@helmholtz-muenchen.de.
2
Max-Planck-Institut für biophysikalische Chemie, Department of Molecular Developmental Biology, Am Faβberg 11, D-37077, Göttingen, Germany. yanjun.xu@helmholtz-muenchen.de.
3
Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, D-85764, Neuherberg, München, Germany. yanjun.xu@helmholtz-muenchen.de.
4
Max-Planck-Institut für biophysikalische Chemie, Research Group Molecular Physiology, Am Faβberg 11, D-37077, Göttingen, Germany.
5
University of Graz, Institute of Molecular Biosciences, Humboldtstrasse 50/2.OG, A-8010, Graz, Austria.
6
Christian-Albrechts University Kiel, Zoology, Molecular Physiology, 24098, Kiel, Germany.
7
Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Kiel, Germany.
8
Max-Planck-Institut für biophysikalische Chemie, Research Group Molecular Physiology, Am Faβberg 11, D-37077, Göttingen, Germany. ronald.kuehnlein@uni-graz.at.
9
University of Graz, Institute of Molecular Biosciences, Humboldtstrasse 50/2.OG, A-8010, Graz, Austria. ronald.kuehnlein@uni-graz.at.
10
BioTechMed Graz, Graz, Austria. ronald.kuehnlein@uni-graz.at.

Abstract

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.

PMID:
31061470
DOI:
10.1038/s41598-019-43327-y
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