Abstract
Glycogen is the major carbohydrate reserve in animals, mainly in the muscle and liver. It is mobilized via glycogenolysis to liberate glucose, which is used for glycolysis/mitochondrial respiration in the muscle to produce ATP, or released into the blood to maintain sugar homeostasis especially when nutrients are scarce. Although glycogen homeostasis is critical for animal physiology, the mechanisms controlling glycogen storage and utilization remain poorly understood. We recently showed that Drosophila FMRFa neuropeptide signaling is required for glycogen homeostasis in the jump muscle, a major tissue of FMRFa receptor (FMRFaR) expression. Here, we report that glycogen accumulation in the flight muscle and fat body also depends on FMRFa signaling, despite the absence of FMRFaR expression in these tissues. In vivo glucose imaging revealed that neither FMRFa nor FMRFaR mutants show deficits in intracellular glucose levels, consistent with a defect in glycogen synthesis or breakdown. Lastly, mutant flies exhibit reduced lifespan when kept on normal or protein-only food, but not on sugar-only food. These findings reveal that Drosophila FMRFa-FMRFaR signaling is a key modulator of systemic glycogen metabolism, thereby influencing survival and fitness in a diet-dependent manner.