Jellyfish and fruit flies shed light on the origin of satiety

What is it about?

Finding food sources is a critical challenge for all animals. Decades’ worth of research has shown that the motivation to feed is controlled by hormones and neuropeptides. These are common in model organisms like humans, mice and fruit flies. Their widespread occurrence suggests a common evolutionary origin, but how ancient it could be remains unclear. To address this, we focused on jellyfish. Jellyfish shared a common ancestor with mammals at least 600 million years ago. However, their bodies are simpler, with diffuse nervous systems sometimes described as nerve nets. Nevertheless, jellyfish are capable of a rich repertoire of behaviors including elaborate foraging strategies, mating rituals, sleep and even learning. Despite their important position in the tree of life, these fascinating creatures remain understudied. For example, almost nothing is known about how they control their food intake. For our research, we used Cladonema, a small jellyfish with branched tentacles that can be raised in our laboratory. These jellyfish regulate how much they eat: hungry animals consume much more prey. To understand the underlying mechanism, we compared gene expression in hungry and fed animals. The feeding state changed the expression levels of many genes, including some that encode neuropeptides. By synthesizing and testing these neuropeptides, we found five that reduced feeding in hungry jellyfish. To understand how such neuropeptides control feeding, we focused on one of them: GLWamide. Detailed behavioral analysis revealed that GLWamide inhibited tentacle shortening, a crucial step for transferring captured prey to the mouth. Interestingly, when we labelled GLWamide, we found that it was present in motor neurons located in the tentacle bases, and feeding increased GLWamide levels. These and additional data led us to conclude that GLWamide is a satiety signal in Cladonema. To address the evolutionary significance of this finding, we looked to other species. We were intrigued by MIP, a neuropeptide that regulates feeding in insects. Fruit flies lacking MIP eat more food, eventually becoming obese. Interestingly, MIP and GLWamide share similarities in their structures, suggesting they are related through evolution. If the functions of GLWamide and MIP have been conserved despite 600 million years of divergence, it should be possible to exchange them. We did just that, first giving MIP to jellyfish. Indeed, MIP reduced Cladonema feeding like GLWamide. Next, we expressed GLWamide in flies that have no MIP. Surprisingly, GLWamide was able to substitute MIP, eliminating these flies’ abnormal over-eating. The simplest conclusion is that the GLWamide/MIP system is functionally conserved in jellyfish and insects. Our work highlights deep evolutionary origins of a conserved satiety signal. We hope that our comparative approach will inspire focused investigation of the role of molecules, neurons and circuits in the regulation of behavior within a wider evolutionary context.

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Photo by Jeffrey Hamilton on Unsplash

Photo by Jeffrey Hamilton on Unsplash

Why is it important?

Public interest in jellyfish has been increasing due to large socio-economic impacts, for example in fishing and power generation. Moreover, there is growing concern about human impacts on marine life, and especially reduction of biodiversity. This could be related with an increase in jellyfish populations. These facts, along with the interesting position of jellyfish in the Tree of Life, have recently sparked great interest in jellyfish and related species. Tools such as CRISPR gene editing and transcriptomics technologies now enable in-depth, mechanistic studies of these exotic non-model organisms. To the best of our knowledge, our study identifies a molecule that controls feeding in jellyfish for the first time. Importantly, it places this finding in a broader context, showing that this molecule can also function in fruit flies. Therefore, it offers both mechanistic and evolutionary insights for feeding regulation in animals. This is important because, as the famous evolutionary biologist Theodosius Dobzhansky once wrote, "Nothing in biology makes sense except in the light of evolution".