LAUSR

recent years a number of additional hormonal systems have been uncovered. In particular, our lab identified Upd2 as the Drosophila Leptin ortholog. Recently, we characterized the mechanism by which Upd2 senses fat in adipose tissues, and showed that Upd2/Leptin secretion occurs via an energy-state sensitive network of proteinaceous compartments, formed by the unconventional secretion component GRASP, on the surface of lipid droplets, regulated via phosphorylation downstream of Glucagon mediated Ca2+ signaling. In addition, we showed that Drosophila muscles, depending on their physiological states, produce a number of systemic factors, such as ImpL2/IGFBP and Myostatin/GDF11. Interestingly, we found that ImpL2, which is produced fromgut tumors, triggers systemic organwasting reminiscent to cachexia by downregulating systemic Insulin levels. The gut also produces a number of hormones produced by enteroendocrine cells (EEs) regulate physiology. For example, we showed that Activin-β (Actβ), an activin ligand is produced in the enteroendocrine cells (EEs) of the midgut, is upregulated by chronic high-sugar diet and signals specifically through Babo to promote AKH/Glucagon action in the fat body, leading to hyperglycemia. Altogether, our work and others, have shown that: 1. Drosophila is an excellent model to dissect organ communications, especially as we have tools for genome scale interrogation of gene functions in organ communication; 2. Many of the regulatory mechanisms are conserved with mammals; 3. A number of human diseases related can be modeled in the fly, including obesity and organ wasting/cachexia.