Study finds hormone controlling appetite comes from starfish ancestor

By Stephen Beech

The hormone-controlling appetite in humans dates back to the ancestors of starfish over half a billion years ago, according to new research.

The discovery could help develop new Ozempic-like weight-loss drugs, say scientists.

A team of biologists at Queen Mary University of London (QMUL) found that the molecule, known as bombesin and which triggers the feeling of being full, is not only present in humans and other vertebrates but also in starfish and their marine relatives.

The research team explained that bombesin, a small peptide, plays a "key" role in regulating hunger by signaling when we’ve had enough to eat.

But its story doesn’t start with humans or even mammals.

The research, published in the journal Proceedings of the National Academy of Sciences (PNAS), shows that bombesin-like neurohormones have been controlling appetite in animals since long before the first vertebrates evolved on Earth.

The name bombesin comes from the fire-bellied toad (Bombina bombina), from whose skin the peptide was first isolated in 1971.

When injected into mammals, bombesin was found to reduce meal size and increase the time between meals.

That led scientists to believe that bombesin-like neurohormones, produced in the brain and gut, are part of the body’s natural system for controlling food intake.

Alongside weight-loss-inducing drugs such as Ozempic, compounds that mimic the action of bombesin are in development for the treatment of obesity.

Professor Maurice Elphick and his team at QMUL, in collaboration with Dr. Olivier Mirabeau at the Institut Pasteur in Paris, set out to explore the evolutionary history of bombesin.

By analyzing the genomes of invertebrate animals, they discovered genes encoding bombesin-like neurohormones in the common starfish and other echinoderms, including sea urchins and sea cucumbers.

Elphick said: “It was a bit like looking for a needle in a haystack.

"But eventually we discovered genes encoding a bombesin-like neurohormone in the genomes of starfish and their relatives.”

The researchers then looked at the function of the starfish bombesin, named ArBN.

Using mass spectrometry, colleagues at the University of Warwick determined the molecular structure of ArBN, allowing it to be chemically synthesized and tested.

Study lead author Dr. Weiling Huang, a former PhD student in Elphick's lab, investigated how ArBN affects starfish feeding behavior.

He explained that starfish have a unique way of eating: they take their stomach out of their mouth to digest prey like mussels and oysters.

Dr. Huang said: “When I tested ArBN, I saw that it caused contraction of the starfish stomach.

“This suggested that ArBN might be involved in stimulating stomach retraction when starfish stop feeding.

"And this is exactly what I found.

"When I injected ArBN into starfish with their stomachs everted, it triggered the stomach to retract back into the mouth.

"What’s more, ArBN also delayed the initiation of feeding, as starfish injected with ArBN took longer to enclose a mussel compared to those injected with water.”

The researchers say the discovery of bombesin’s ancient role in appetite regulation sheds light on the evolutionary origins of feeding behavior in animals.

Elphick said: “We can infer that this function extends back half a billion years to the common ancestor of starfish, humans, and other vertebrates."

As well as the development of new weight-loss-promoting drugs, the team say their findings could have other practical applications.

Elphick added: “One of the consequences of climate change is that some starfish species are invading cooler waters where shellfish are cultivated for human consumption.

“Discovering molecules that inhibit feeding in starfish could be useful in managing these invasions.”