Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila

摘要: Neurofibromatosis type 1 (NF1) is a genetic disorder predisposing patients to range of features, the most characteristic which include areas abnormal skin pigmentation and benign tumors associated with peripheral nerves, termed neurofibromas. Less common, but more serious symptoms also malignant nerve sheath tumors, other malignancies, learning disabilities. The NF1 gene encodes neurofibromin, large protein that functions as negative regulator Ras signaling mediates pleiotropic cellular organismal function. Recent evidence suggests may regulate metabolism, though mechanisms are unknown. Here we show Drosophila ortholog NF1, dNf1 regulates metabolic homeostasis in fruit flies by functioning within discrete brain circuit. Loss increases rate feeding, enhances starvation susceptibility, decreases lipid stores while increasing turnover rate. increase independent locomotor activity (grooming), maps subset neurons ventral nervous system. feeding effects due loss same set neurons, suggesting increased be compensatory effect driven turnover. Finally, GAP-related domain neurofibromin required for normal demonstrating downstream effects. These data demonstrate via neuronal mechanisms, suggest systemic alterations represent pathophysiological mechanism provide platform investigating role homeostasis.