Cardiaca adipokinetic hormone and hedgehog signaling combine to generate intracellular waves of Ca++ in starved Drosophila melanogaster fat body

The Drosophila melanogaster fat body combines the functions of the vertebrate liver and fat. It plays a central role in metabolism where it integrates information about nutritional status to regulate fat utilization. During feeding, signaling through the Insulin Receptor causes lipogenesis, while fasting leads to signaling through the cardiaca Adipokinetic Hormone Receptor (AKHR) and mobilization of lipid stores. Here we examine intracellular calcium levels in the fat body during fasting. In fasting early third instar larvae, spikes of intracellular calcium are generated in the fat body lobes on either side of the brain. These spikes propagate through a narrow connection into the main lobes of the fat body that lie along the length of the larva. The spikes of intracellular Ca++ are dependent on the corpora cardiaca AKH expressing neurons and AKHR. Unexpectedly, the spikes also require Hedgehog (Hh) signaling from the midgut enterocytes and within the fat body. When Hh signaling is blocked, the Ca++ levels in the fat body are elevated and the spiking behavior lost. Hh signaling appears to regulate fat body intracellular Ca++ using both the transcription factor Cubitus interruptus and the trimeric G protein Gi. AKH/Hh signaling in the fat body lobes on either side of the brain appears to function as a pulse generator to initiate Ca++ spikes that then propagate through the main lobes of the fat body. These studies show how signaling from the brain and the midgut and within the fat body are integrated to regulate a key intracellular second messenger.