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Citation
Zhao, P., Huang, P., Xu, T., Xiang, X., Sun, Y., Liu, J., Yan, C., Wang, L., Gao, J., Cui, S., Wang, X., Zhan, L., Song, H., Liu, J., Song, W., Liu, Y. (2021). Fat body Ire1 regulates lipid homeostasis through the Xbp1s-FoxO axis in Drosophila.  iScience 24(8): 102819.
FlyBase ID
FBrf0250195
Publication Type
Research paper
Abstract

The endoplasmic reticulum (ER)-resident transmembrane protein kinase/RNase Ire1 is a conserved sensor of the cellular unfolded protein response and has been implicated in lipid homeostasis, including lipid synthesis and transport, across species. Here we report a novel catabolic role of Ire1 in regulating lipid mobilization in Drosophila. We found that Ire1 is activated by nutrient deprivation, and, importantly, fat body-specific Ire1 deficiency leads to increased lipid mobilization and sensitizes flies to starvation, whereas fat body Ire1 overexpression results in the opposite phenotypes. Genetic interaction and biochemical analyses revealed that Ire1 regulates lipid mobilization by promoting Xbp1s-associated FoxO degradation and suppressing FoxO-dependent lipolytic programs. Our results demonstrate that Ire1 is a catabolic sensor and acts through the Xbp1s-FoxO axis to hamper the lipolytic response during chronic food deprivation. These findings offer new insights into the conserved Ire1 regulation of lipid homeostasis.

PubMed ID
PubMed Central ID
PMC8333185 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    iScience
    Title
    iScience
    ISBN/ISSN
    2589-0042
    Data From Reference