The fly sensor is found in the fat body—an organ similar in nutritional storage and endocrine functions to the human liver. Léopold's group now shows that the fat body warns other larval tissues of limited nutrient supply by monitoring amino acid levels.
Growth defects were induced throughout the fly when the activity of an amino acid transporter, called slimfast, was blocked in the fat body, whereas defects remained localized when it was blocked elsewhere. Growth was particularly limited in endoreduplicating tissues (ERT)—mostly juvenile tissue that will disappear at the end of the larval stage. Growth in the future adult tissue, the imaginal discs, was less affected.
The fat body probably sends its starvation signal via the insulin/insulin-like growth factor (IGF) pathway. Amino acid starvation inhibited fat body expression of dALS, a protein homologous to a vertebrate protein that circulates with and stabilizes IGFs in the blood. Peripheral tissues had reduced IGF responses, indicated by lower PI3K activity. In contrast, the imaginal discs retained PI3K signaling, possibly through local IGF production. This may protect important organs under poor nutritional conditions. “In the larva, quite a lot of nutrients are stored by the animal” says Léopold. “If ERT growth is blocked, [the fly] can use these leftovers in the future adult tissues.” Vertebrate homologues of IGF and ALS are secreted by the liver, suggesting that this organ may have analogous nutrient sensing functions in vertebrates. ▪