Brain adiponectin signaling controls peripheral insulin response in Drosophila

The brain plays a key role in energy homeostasis, detecting circulating hormones from peripheral organs, nutrients, and metabolites, and integrating this information to control food intake and energy expenditure. However, the signals mediating communication between peripheral organs and brain are largely unknown. Here, we show that a group of neurons in the Drosophila larval brain expressing the adiponectin receptor (AdipoR) control systemic growth and metabolism. We identify glucose-regulated protein 78 (Grp78) as a circulating ligand for AdipoR. Grp78 is produced by fat cells in response to dietary sugar and modulates the activity of AdipoR-positive neurons. The terpenoid juvenile hormone (JH) serves as an effector for brain AdipoR signaling, reducing the levels of insulin signaling in peripheral organs. In conclusion, we identify a neuroendocrine axis whereby AdipoR neurons control systemic insulin responses by modulating peripheral JH function.