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Citation
Molaei, M., Vandehoef, C., Karpac, J. (2019). NF-κB Shapes Metabolic Adaptation by Attenuating Foxo-Mediated Lipolysis in Drosophila.  Dev. Cell 49(5): 802--810.e6.
FlyBase ID
FBrf0242584
Publication Type
Research paper
Abstract

Metabolic and innate immune signaling pathways have co-evolved to elicit coordinated responses. However, dissecting the integration of these ancient signaling mechanisms remains a challenge. Using Drosophila, we uncovered a role for the innate immune transcription factor nuclear factor κB (NF-κB)/Relish in governing lipid metabolism during metabolic adaptation to fasting. We found that Relish is required to restrain fasting-induced lipolysis, and thus conserve cellular triglyceride levels during metabolic adaptation, through specific repression of ATGL/Brummer lipase gene expression in adipose (fat body). Fasting-induced changes in Brummer expression and, consequently, triglyceride metabolism are adjusted by Relish-dependent attenuation of Foxo transcriptional activation function, a critical metabolic transcription factor. Relish limits Foxo function by influencing fasting-dependent histone deacetylation and subsequent chromatin modifications within the Bmm locus. These results highlight that the antagonism of Relish and Foxo functions are crucial in the regulation of lipid metabolism during metabolic adaptation, which may further influence the coordination of innate immune-metabolic responses.

PubMed ID
PubMed Central ID
PMC6548632 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Dev. Cell
    Title
    Developmental Cell
    Publication Year
    2001-
    ISBN/ISSN
    1534-5807 1878-1551
    Data From Reference