Neuronal E93 regulates metabolic homeostasis

Abstract

AbstractMetamorphosis 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 neuronalE93, a transcription factor essential for metamorphosis, regulates the adult metabolism and circadian rhythm inDrosophila melanogaster. WhenE93is 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 ofE93action. Knockdown of the ecdysone receptor specifically in MIP neurons partly phenocopies the MIP neuron-specific knockdown ofE93suggesting the steroid signal coordinates adult metabolism viaE93. The circadian disruption caused by neuronal knockdown ofE93is also observed whenE93is knockdown in GABA and MIP neurons. Based on these results we suggest that neuronalE93is a key switch for metabolic transition representing an intersectional node between metabolism and circadian biology.