Neuronal E93 regulates metabolic homeostasis

Metamorphosis is a transition from growth to reproduction, through which an animal adopts adult behavior and metabolism. Yet the mechanisms underlying the switch is unclear. Here we report that neuronal E93, a transcription factor essential for metamorphosis, regulates the adult metabolism and circadian rhythm in Drosophila melanogaster. When E93 is specifically knocked down in neurons, the flies 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. Knockdown of the ecdysone receptor specifically in MIP neurons partly phenocopies the MIP neuron-specific knockdown of E93 suggesting the steroid signal coordinates adult metabolism via E93. The circadian disruption caused by neuronal knockdown of E93 is also observed when E93 is knockdown in GABA and MIP neurons. Based on these results we suggest that neuronal E93 is a key switch for metabolic transition representing an intersectional node between metabolism and circadian biology.