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Citation
Shen, R., Wang, B., Giribaldi, M.G., Ayres, J., Thomas, J.B., Montminy, M. (2016). Neuronal energy-sensing pathway promotes energy balance by modulating disease tolerance.  Proc. Natl. Acad. Sci. U.S.A. 113(23): E3307--E3314.
FlyBase ID
FBrf0232611
Publication Type
Research paper
Abstract

The starvation-inducible coactivator cAMP response element binding protein (CREB)-cAMP-regulated transcription coactivator (Crtc) has been shown to promote starvation resistance in Drosophila by up-regulating CREB target gene expression in neurons, although the underlying mechanism is unclear. We found that Crtc and its binding partner CREB enhance energy homeostasis by stimulating the expression of short neuropeptide F (sNPF), an ortholog of mammalian neuropeptide Y, which we show here is a direct target of CREB and Crtc. Neuronal sNPF was found to promote energy homeostasis via gut enterocyte sNPF receptors, which appear to maintain gut epithelial integrity. Loss of Crtc-sNPF signaling disrupted epithelial tight junctions, allowing resident gut flora to promote chronic increases in antimicrobial peptide (AMP) gene expression that compromised energy balance. Growth on germ-free food reduced AMP gene expression and rescued starvation sensitivity in Crtc mutant flies. Overexpression of Crtc or sNPF in neurons of wild-type flies dampens the gut immune response and enhances starvation resistance. Our results reveal a previously unidentified tolerance defense strategy involving a brain-gut pathway that maintains homeostasis through its effects on epithelial integrity.

PubMed ID
PubMed Central ID
PMC4988575 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Breakpoints of CrebB[Delta400] deletion.
Thomas, 2017.7.12, Breakpoints of CrebB[Delta400] deletion. [FBrf0236022]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference