The Origins of Hunger Regulation | TS Digest

Neuropeptides, small proteins released by the nervous system, regulate how much food animals eat. To find out how long these molecules have been playing this role, Vladimiros Thoma, an assistant professor at Tohoku University, turned his attention to jellyfish. “Jellyfish and also other animals called comb jellies are studied as candidates for the origins of neurons,” Thoma explained, making them perfect models for investigating that question.  

Using the jellyfish Cladonema pacificum, Thoma and his colleagues discovered a peptide that controls feeding both in jellyfish and fruit flies, animals that shared a common ancestor millions of years ago. Their findings suggest deep evolutionary roots for the role of neuropeptides in appetite regulation.1 

To identify the molecules regulating Cladonema’s appetite, the team starved jellyfish for about 50 hours and compared the gene expression profiles of starved and recently fed jellyfish. They found that feeding changed the expression of several genes, including those encoding neuropeptides. After screening the ability of these molecules to control food intake, they found five feeding suppressors, among which was the peptide GLWamide.

     The image shows the base of a jellyfish’s tentacle and the animal’s eyelet. The neurons expressing the peptide of interest are shown in green, and the cell nuclei are labeled in magenta. The jellyfish is against a black background. 

Researchers labeled the peptide GLWamide (green) and cell nuclei (magenta) and found that GLWamide is expressed in neurons in the tentacle and in those surrounding the jellyfish eyelet (black circle).


“These Wamide peptides were originally discovered in insects,” said Meet Zandawala, a neuropeptide researcher at the University of Nevada, Reno, who was not involved in the study. “It is quite interesting to find these peptides in such [simple] animals.” 

The team also showed that GLWamide is expressed in neurons in jellyfish tentacles, and that it inhibited the tentacle contraction movement to suppress feeding. 

Next, the researchers tested whether GLWamide worked similar to myoinhibitory peptide (MIP), a known appetite regulator in fruit flies. They bathed jellyfish with MIP and generated transgenic flies that expressed GLWamide but lacked MIP. They found that MIP reduced the jellyfish’s shrimp intake, while GLWamide decreased the number of times flies stuck out their proboscises to ingest a drop of sugary water. 

“This signal is evolutionarily conserved. It is also in the flies, and it seems to work the same way,” Thoma explained. “It is kind of striking that over millions of years, you still have a very similar system.” 

Zandawala believes that an important next step is to identify the target of the jellyfish peptide. Scientists may be able to investigate this and other questions as they develop tools to study this organism, Thoma said. “It has a bright future ahead.”


  1. Thoma V, et al. Proc Natl Acad Sci U S A. 2023;120(15):e2221493120.

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