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Citation
Kim, D.H., Shin, M., Jung, S.H., Kim, Y.J., Jones, W.D. (2017). A fat-derived metabolite regulates a peptidergic feeding circuit in Drosophila.  PLoS Biol. 15(3): e2000532.
FlyBase ID
FBrf0235153
Publication Type
Research paper
Abstract

Here, we show that the enzymatic cofactor tetrahydrobiopterin (BH4) inhibits feeding in Drosophila. BH4 biosynthesis requires the sequential action of the conserved enzymes Punch, Purple, and Sepiapterin Reductase (Sptr). Although we observe increased feeding upon loss of Punch and Purple in the adult fat body, loss of Sptr must occur in the brain. We found Sptr expression is required in four adult neurons that express neuropeptide F (NPF), the fly homologue of the vertebrate appetite regulator neuropeptide Y (NPY). As expected, feeding flies BH4 rescues the loss of Punch and Purple in the fat body and the loss of Sptr in NPF neurons. Mechanistically, we found BH4 deficiency reduces NPF staining, likely by promoting its release, while excess BH4 increases NPF accumulation without altering its expression. We thus show that, because of its physically distributed biosynthesis, BH4 acts as a fat-derived signal that induces satiety by inhibiting the activity of the NPF neurons.

PubMed ID
PubMed Central ID
PMC5369665 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Biol.
    Title
    PLoS Biology
    Publication Year
    2003-
    ISBN/ISSN
    1545-7885 1544-9173
    Data From Reference
    Alleles (42)
    Genes (14)
    Natural transposons (2)
    Insertions (9)
    Experimental Tools (3)
    Transgenic Constructs (32)