Affiliation: Texas A&M Health Science Center, Bryan, TX
Keywords: b. neuropeptides; b. metabolism
Neuropeptides and their cognate receptors are critical molecular effectors that modulate many physiological processes and behavioral outputs. We recently reported that Glucose-6-phosphatase, one of the key gluconeogenic enzymes, is exclusively expressed in a small subset of about 30 large neurosecretory cells in the CNS of the fruit fly. Moreover, we demonstrated that neural activities of G6P neurons, but not glucose production per se, is critical for glucose homeostasis. These neurons are essential to maintain systemic glucose homeostasis, yet their identities are largely unknown. Here we show that G6P-GAL4 neurons express at least five distinct neuropeptides such as NPF, Orcokinin, PDF, FMRFa and Nplp1. Neural silencing of each class of neuropeptide neurons showed that only the FMRFa-producing neurons in the thoracic ganglion are essential for glucose homeostasis. FMRFa mutants show a similar hypoglycemic phenotype as G6P mutants, suggesting that G6P maintains systemic glucose homeostasis via FMRFa signaling.To support this idea, we measured secretory capabilities of FMRFa neurons using a neuropeptide reporter, a mammalian atrial natriuretic peptide fused to GFP (ANF-GFP). We found that G6P mutants show significantly lower amounts of ANF-GFP in the hemolymph, compared to G6P wildtype flies. These results indicate that G6P cell-autonomously increases circulating neuropeptide amounts by facilitating neuropeptide processing, transport and/or release. Taken together, our data suggest that G6P maintains systemic glucose homeostasis by increasing FMRFa amounts in the hemolymph.