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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipose Tissue / metabolism*
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Adipose Tissue / pathology
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Animals
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Aspartate Aminotransferase, Cytoplasmic / genetics
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Aspartate Aminotransferase, Cytoplasmic / metabolism
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Calcium / metabolism*
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Calcium Signaling
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism
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Disease Models, Animal
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Drosophila Proteins / antagonists & inhibitors
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster
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Energy Metabolism / genetics
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Female
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Gene Expression Regulation
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Homeostasis / genetics
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Humans
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Hyperphagia / genetics*
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Hyperphagia / metabolism
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Hyperphagia / pathology
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Insect Hormones / genetics*
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Insect Hormones / metabolism
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Ion Transport
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Lipid Metabolism / genetics
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Malate Dehydrogenase / genetics
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Malate Dehydrogenase / metabolism
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Male
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Obesity / genetics*
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Obesity / metabolism
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Obesity / pathology
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Oligopeptides / genetics*
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Oligopeptides / metabolism
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Pyrrolidonecarboxylic Acid / analogs & derivatives*
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Pyrrolidonecarboxylic Acid / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Stromal Interaction Molecule 1 / antagonists & inhibitors
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Stromal Interaction Molecule 1 / genetics*
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Stromal Interaction Molecule 1 / metabolism
Substances
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Aralar protein, Drosophila
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Calcium-Binding Proteins
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Drosophila Proteins
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Insect Hormones
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Isoenzymes
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Oligopeptides
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RNA, Small Interfering
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Stim protein, Drosophila
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Stromal Interaction Molecule 1
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DAKH peptide
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Malate Dehydrogenase
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Aspartate Aminotransferase, Cytoplasmic
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Calcium
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Pyrrolidonecarboxylic Acid