Jellyfish and flies use the same hormone when they’ve had enough to eat

Image of a jellyfish near the surface of the ocean.
Enlarge / A Moon jellyfish.

The sensation of hunger seems pretty simple on the surface, but behind the scenes, it involves complicated networks of sending and signaling, with multiple hormones that influence whether we decide to have another serving or not. The ability to know when to stop eating appears to be widespread among animals, suggesting that it might have deep evolutionary roots.

A new study suggests that at least one part of the system goes back to nearly the origin of animals. Researchers have identified a hormone that jellyfish use to determine when they're full and stop eating. And they found that it's capable of eliciting the same response in fruit flies, suggesting the system may have been operating in the ancestor of these two very distantly related animals. That ancestor would have lived prior to the Cambrian.

Feeding the fish (or jellyfish)

Given they lack any obvious equivalents to a mouth, it might seem like it would be tough to determine whether a jellyfish is even eating, much less hungry. But a team of Japanese researchers showed that the jellyfish species Cladonema pacificum has a bunch of stereotypical behaviors while feeding, including that their tentacles latch onto prey and that they then withdraw the tentacle into the bell so that the prey can be digested. And, if you keep feeding the jellyfish brine shrimp, eventually this process will slow, indicating that the animal is sensing it is well fed. (There's a movie available of the jellyfish feeding.)

To find out how this was controlled, the researchers dissected the central core of the jellyfish, which contains its digestive organs, and the bell, which contains much of the animal's nerve net. They then looked at which genes were active in these tissues when the animal was either starved or satiated. And, just to be sure there was no confusion, they also generated a complete list of the genes active in the brine shrimp that were fed to the jellyfish. From this, they developed a list of potential hormones that were active when the animal was fed but not when it was hungry.

All told, they came up with 43 genes that encode small molecules that could potentially act as a hormone. These are typically normal-sized proteins that have a repeating sequence such that they can be chopped up to form a collection of short amino acid chains called peptides. Sometimes, these peptides are modified further before being used as hormones.

The researchers chemically synthesized all 43 genes and tested whether they could modify feeding behavior. They found five that did; four of them were activated after an animal had been fed to the point where it stopped feeding.

For the study, the researchers chose to focus on one of these, with the unfortunate name (N)GPPGLWamide (they referred to it as GLWa, and I'll do the same). Treating jellyfish with GLWa suppressed tentacle contraction during feeding to about the same degree as feeding the animals multiple brine shrimp. It was also interesting because the gene that encodes it is found in a large range of Cnidarians, the group of radially symmetric organisms that include jellyfish, corals, and anemones. That suggests it may play a role in regulating appetite in various species.

Here, there, and everywhere?

But relatives of GLWa aren't limited to Cnidarians. More distantly related versions are found widely in animals. That's no guarantee, however, that the peptides are used for the same processes. So, to find out what GLWa might be doing elsewhere, the researchers turned to a convenient research animal, the fruit fly Drosophila, which has a GLWa relative called MIP.

Flies treated with the hormone also show a suppression of feeding behavior. And those that lack the gene that encodes the hormone continue to feed even if they've already had a lot to eat. So, the fly equivalent seems to be doing the same things.

But the striking thing is that the jellyfish version of the hormone worked in flies. You could replace the gene encoding the fly version of the hormone with the jellyfish gene, and the flies would show normal regulation of feeding. Or you can just treat the flies with the jellyfish hormone and suppress their feeding.

Fruit flies belong to the group Bilateria, which includes all animals with a defined left and right side. We know that Bilaterians and Cnidarians branched off from a common ancestor very early in the history of animal life and that this must have happened prior to the origin of most present animal groups, which happened in the Cambrian—there's clear evidence of Bilaterian animals prior to the Cambrian.

The fact that the hormone works in such widely separated species suggests that it may have originated very early in the history of animal life. The researchers also note that there appear to be relatives of this hormone in animals that branched off even earlier, such as sponges, which don't appear to have feeding behavior at all. There are even hints of a similar gene in the cells that are most closely related to animals, called choanoflagellates.

One possible explanation is that this system was regulating feeding behavior at the very start of the history of animal life on Earth. One argument against this, however, is that organisms like sponges don't seem to have any feeding behavior, so it's not clear what a hormone like this would do in these animals. The second caution is that we don't know how this hormone acts. Typically, they bind to some sort of receptor, but this research team hasn't identified the receptor for GLWa, so it's impossible to tell if the same signaling system is used in both flies and jellyfish, or the species' respective hormones happen to produce the same response through completely different mechanisms.

There are many potential ways to get a better picture of what's happening with the origin of appetite control. So, the research team here will have no shortage of experiments to do to follow up on this work.

PNAS, 2023. DOI: 10.1073/pnas.2221493120  (About DOIs).