Wednesday 26 October 2016

Cave fish clues for human obesity

Published 13/07/2015 | 20:31

Blind cavefish are genetically wired for big appetites in the same way as obese humans, research has shown (Harvard Medical School/PA)
Blind cavefish are genetically wired for big appetites in the same way as obese humans, research has shown (Harvard Medical School/PA)

A fat binge-eating fish is genetically wired for big appetites in the same way as obese humans, research has shown.

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Scientists believe the Mexican cave fish, whose apparent greed allows them to survive long periods without food, can help explain some of the mysteries of over-eating.

The fish live in remote caves in north-eastern Mexico where food only becomes available about once a year when it is swept in by floods.

Over hundreds of thousands of years, the cave fish have adapted to the darkness by losing their eyes - and learned how to resist starvation.

Lead researcher Professor Clifford Tabin, from Harvard Medical School in the US, said: "We all know that people have different metabolisms that lead to their gaining weight under different amounts of eating.

" The work with the cave fish gives us an example in a natural setting of why and how metabolisms evolved to be different. Some of the mechanisms we see in the fish may well have implications for human metabolism and therefore human health."

Like humans with inherited obesity, most of the fish were found to have mutations in the MC4R gene - known to be at the heart of appetite regulation.

Laboratory mice lacking MC4R are severely obese and constantly hungry. In humans, the gene's activity is controlled by the appetite-suppressing hormone leptin and insulin.

Tests showed that after two months without food, Mexican cave fish lost half as much weight as another version of the same species that lives above ground.

After three months, the cave fish continued to thrive, while their surface-dwelling cousins began to starve and die.

Co-author Dr Nicolas Rohner, a researcher in Prof Tabin's laboratory, said: "These fish are very, very fat - much fatter than surface fish. And although they are active, their metabolism is slower."

The study, published in the journal Proceedings of the National Academy of Sciences, showed that MC4R activity was reduced in the cave fish, taking the brakes off appetite suppression.

Mutations in the gene that stimulate binge-eating have proved advantageous to the fish - and may also have benefited human ancestors long ago, the scientists believe.

In times of food scarcity, an ability to consume a lot of calories at once and store them as fat could have been a life saver.

Dr Rohner pointed out that even before the modern obesity epidemic, humans as a species were "very fat".

He added: "There was selection for that in our evolution, but we don't know why. Understanding how these fish became fat might eventually help us understand how we did.

"That's something that bothers me a lot - that we have to fight against this urge to eat and drink sweet and fatty things all the time and that it's because of our evolutionary history.

"The possibility that we can find out why that is, perhaps by using these cave fish as a model system, makes me confident that one day we will find a way to resist that urge."

The team is convinced that other genes also play a role in the cave fish. MC4R mutations do not fully explain the fish's increase in appetite, or their fatty livers.

A search is now on for additional mutations that could shed further light on human metabolism and obesity.

Press Association

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