A nutrient-responsive hormonal circuit controls energy and water homeostasis in Drosophila

The regulation of systemic energy balance involves the coordinated activity of specialized organs, which control nutrient uptake, utilization and storage to promote metabolic homeostasis during environmental challenges. The humoral signals that drive such homeostatic programs are largely unidentified. Here we show that three pairs of central neurons in adult Drosophila respond to internal water and nutrient availability by releasing Capa-1 and -2 hormones that signal through the Capa receptor (CapaR) to exert systemic metabolic control. Loss of Capa/CapaR signaling leads to intestinal hypomotility and impaired nutrient absorption, which gradually deplete internal nutrient stores and reduce organismal lifespan. Conversely, hyperactivation of the Capa circuitry stimulates fluid and waste excretion. Furthermore, we demonstrate that Capa/CapaR regulates energy metabolism by modulating the release of the glucagon-like adipokinetic hormone, which governs lipolysis in adipose tissue to stabilize circulating energy levels. Altogether, our results uncover a novel inter-tissue program that plays a central role in coordinating post-prandial responses that are essential to maintain adult viability.