The sensation of hunger seems pretty simple on the surface, but behind the scenes, it involves a complex network of transmissions and signals, multiple hormones that influence whether we decide to have another serving. The ability to know when to stop eating appears to be widespread among animals, suggesting that it may have deep evolutionary roots.
A new study suggests that at least part of the system goes back to its animal origins. Researchers have identified a hormone that jellyfish use to determine when they are full and stop eating. And they found that it was able to elicit the same response in fruit flies, suggesting that the system was at work in these two very distant animal ancestors. That ancestor lived before the Cambrian.
Feeding fish (or jellyfish).
Because they lack any obvious equivalent to a mouth, it might seem that it would be difficult to determine if a jellyfish is even eating, much less hungry. But a group of Japanese researchers have shown the species of jellyfish Cladonema pacificum They have a set of stereotypical behaviors when feeding, including that their tentacles cling to the prey and then they retract the tentacle into the baleen to allow the prey to be digested. And, if you continue to feed the jellyfish brine shrimp, eventually this process will slow down, indicating that the animal feels that it is well fed. (There a movie available for feeding on jellyfish.).
To find out how this was regulated, the researchers dissected the jellyfish’s central core, which houses its digestive organs, and the bell, which houses most of the animal’s nerve net. They then looked at which genes were active in these tissues when the animal was either hungry or satiated. And, to make sure there was no confusion, they also made a complete list of the genes active in the brine shrimp fed the jellyfish. From this, they created a list of possible hormones that were active when the animal was fed but not when it was starving.
All told, they came up with 43 genes that encode small molecules that could potentially act as hormones. They are usually normal-sized proteins that have repeating sequences that can be cut to form a collection of short amino acid chains called peptides. Sometimes, these peptides are further modified before being used as hormones.
The researchers chemically synthesized all 43 genes and tested whether they could change feeding behavior. They found that five; Four of them were activated when an animal was stopped feeding.
For the study, the researchers chose to focus on one with the unfortunate name (N)GPPGLWamide (they refer to it as GLWa, and I’ll do the same). Treating jellyfish with GLWa fed animals multiple brine shrimp at approximately the same dose as feeding tamarind contractions. It was also interesting because the gene that encodes it is found in a large range of cnidarians, a group of radially symmetrical organisms that includes jellyfish, corals and anemones. This suggests that it may play a role in appetite regulation in various species.
Is it here and everywhere?
But relatives of GLWa are not limited to Cnidarians. More distantly related versions are widely found in animals. This is no guarantee, however, that the peptides are used for the same process. So, to find out what GLWa was doing elsewhere, the researchers turned to a convenient research animal, the fruit fly Drosophilawhich has a GLWa relative called MIP.
Flies treated with hormones also showed suppression of feeding behavior. And those who lack the gene that encodes the hormone continue to eat even though they have already eaten a lot. So, the Fly equivalent seems to be doing the same thing.
But the surprising thing was that the jellyfish version of the hormone worked in flies. You can replace the gene encoding the fly version of the hormone with the jellyfish gene and the flies will show normal feeding patterns. Or you can treat the flies with jellyfish hormones 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 this must have happened before the origin of most current animal groups, which happened in the Cambrian – there is clear evidence of bilaterians before that. Cambrian
The fact that the hormone works in such widely diverged species suggests that it may have originated very early in animal life history. The researchers also noted that the hormone appears to have relatives in animals that branched off earlier, such as sponges, which appear to have no feeding behavior at all. There are even indications of a similar gene in cells most closely related to animals, called choanoflagellates.
One possible explanation is that this system was controlling feeding behavior very early in the history of animal life on Earth. An argument against this, however, is that organisms such as sponges do not seem to have any feeding behavior, so it is unclear what such hormones would do in these organisms. The second caveat is that we do not know how these hormones work. Normally, they bind to some type of receptor, but this research team couldn’t identify a receptor for GLWa, so it’s impossible to say whether both flies and jellyfish use the same signaling system or whether the species produce corresponding hormones. Same reaction through a completely different process.
There are many possible ways to get a better picture of what is happening with the source of appetite control. So, there will be no shortage of experiments for the research team here to pursue this work.
PNAS, 2023. DOI: 10.1073/pnas.2221493120 (Regarding DOI).
