Neuronal E93 regulates metabolic homeostasis

We report a novel function of E93, a transcriptional factor essential for metamorphosis, in the metabolic and circadian regulation of Drosophila melanogaster . When E93 is specifically knocked down in neurons, flies exhibit a systemic dysregulation of metabolic homeostasis. They become hyperphagic and obese with increased energy stores and disrupted circadian rhythms. A screen of Gal4 lines targeting subsets of neurons and endocrine cells identified neurons producing GABA and myoinhibitory peptide (MIP) as the main sites of E93 action. Inhibition of GAL4 by a GAL80 repressor specific to MIP neurons partially but significantly reverses the neuronal E93 knockdown phenotype. Knockdown of the ecdysone receptor, which acts upstream of E93 , specifically in MIP neurons partly phenocopies the MIP neuron-specific knockdown of E93 . Based on these results we suggest that E93 , essential for metamorphosis, is a key switch for the metabolic transition acting in the neurons. ### Competing Interest Statement The authors have declared no competing interest.