Long-term flight depends heavily on intensive energy metabolism in animals; however, the neuroendocrine mechanisms underlying efficient substrate utilization remain elusive. Here, we report that the adipokinetic hormone/corazonin-related peptide (ACP) can facilitate muscle lipid utilization in a famous long-term migratory flighting species, Locusta migratoria. By peptidomic analysis and RNAi screening, we identified brain-derived ACP as a key flight-related neuropeptide. ACP gene expression increased notably upon sustained flight. CRISPR/Cas9-mediated knockout of ACP gene and ACP receptor gene (ACPR) significantly abated prolonged flight of locusts. Transcriptomic and metabolomic analyses further revealed that genes and metabolites involved in fatty acid transport and oxidation were notably downregulated in the flight muscle of ACP mutants. Finally, we demonstrated that a fatty-acid-binding protein (FABP) mediated the effects of ACP in regulating muscle lipid metabolism during long-term flight in locusts. Our results elucidated a previously undescribed neuroendocrine mechanism underlying efficient energy utilization associated with long-term flight.
Keywords: FABP; flight-related lipid metabolism; genetics; genomics; locust; metabolome; neuropeptide; neuropeptidome; neuroscience.
Flight allows insects to find food or seek a better environment. Some insects have developed the ability of ‘long-term flight’, which allows them to make continuous journeys over large distances. For example, one locust species regularly crosses the Red Sea which is up to 300 km wide – a spectacular feat for insects only a few inches long. However, flight is an energy-intensive activity, and insects’ muscles need the right sort of chemical fuel to work properly. Previous work has shown that this ‘fuel consumption’ is highly dynamic and happens in two stages. First, immediately after take-off, the muscles rapidly consume carbohydrates (sugars); then, during the prolonged phase of the flight, muscles switch to exclusively consume lipids (fats). How the flight muscles ‘know’ when to start using fats for energy remains largely unclear. It has been suggested that this switch may involve hormone-like chemicals made in the brain called neuroendocrine peptides. Hou et al. therefore set out to test this hypothesis, using the locust species Locusta migratoria as a representative migratory insect. Initial experiments used an abundance detection technique to determine which of the neuroendocrine peptides were active in adult locusts. Further analysis, looking specifically at locusts that had just been flying, revealed that the gene for a peptide called ACP became much more active after one hour of continuous flight. Further evidence that the ACP hormone could indeed be helping to power long-term flight came from locusts with a mutated, ‘switched-off’ version of the gene. These insects could only fly for half the time, and half the distance, compared to locusts that did not have mutations in the gene for ACP. Biochemical studies of the ACP mutant locusts confirmed that their flight muscle cells could not transport and break down fatty acids normally. These experiments also showed that ACP was acting through a type of carrier protein called FABP, which is present in many different insects and normally ‘ferries’ lipids to the places they are needed. These findings shed new light on the biological mechanisms that control long-term flight in migratory insects. The ability to move over long distances is key to the outbreak of locust plagues, which in turn cause widespread crop damage around the world. Hou et al. therefore hope that this knowledge will one day help develop effective strategies for locust pest control.
© 2021, Hou et al.