Barbecues and clambakes. Ice cream and berry pies. Summer is the season of food, food and more food.
Is there a way to binge and still stay healthy?
For answers, look far underground, say scientists, to the denizens of darkness: blind cavefish.
Biologists studied blind cavefish, Astyanax mexicanus, living in freshwater pools in deep caves in Mexico. The researchers compared the cavefish with their surface-dwelling piscine relatives, which have retained the ability to see.
In the caves’ sunless, pitch-black environment, no primary producers like plants exist. “So cave inhabitants rely entirely on food chains with origins on the outside,” says geneticist Clifford Tabin of Harvard Medical School in Boston, Mass., who led the investigation. The results were published on July 13, 2015, in the journal Proceedings of the National Academy of Sciences.
How do blind cavefish get their meals? Mostly through seasonal flooding when rivers bring tidbits to the caves, and from what cave-roosting bats leave behind. “As a consequence,” says Tabin, “the food supply is very infrequent.”
Staying alive…and satiated
To deal with the challenge of existing on little more than intermittent smorgasbords, cavefish survive by constantly chowing down when food is around, dramatically increasing their body fat. “The fish are very fat, much fatter than their surface-dwelling kin,” says geneticist Nick Rohner, also of Harvard Medical School.
Cavefish store as much fat as possible to tide them over until the next feast. “By doing that, blind cavefish have adapted to cycles of starvation and binge-eating,” says Tabin.
It turns out, he and colleagues discovered, that the fish share a genetic propensity for an insatiable appetite with many obese humans. Foraging cavefish–and some people who find it a trial to avoid a refrigerator–have a mutation in a gene called MC4R (melanocortin 4 receptor).
“People have different metabolisms that lead to weight gain under different amounts of eating,” says Tabin. “This work with cavefish gives us an example in a natural setting of why and how such metabolisms evolved. Some of the mechanisms we see in these fish have implications for human metabolism and health.”
Feast or famine far below
Blind cavefish can withstand months without sustenance by burning fat slowly.
In lab experiments with cavefish and their surface counterparts, after two months without food, the cavefish lost half as much weight as the surface fish. After three months with no food, the cavefish were still doing swimmingly. The surface fish, however, were beginning to die.
Cavefish have higher triglyceride levels than do surface fish. Despite that and weight gain, cavefish live relatively long, healthy lives. The scientists are looking into how that’s possible, so they can develop new ways of treating people struggling with obesity.
The researchers focused their efforts on leptin, a hormone made by fat cells; it helps inhibit hunger. Leptin levels are linked with weight gain in many species, including humans.
Obese fish and overweight humans: sharing genetics
The biologists analyzed DNA from cavefish and their surface cousins to uncover genetic differences in metabolism, body weight and appetite. Most of the cavefish have mutations in the MC4R gene; the surface fish do not.
“When we diet or change how much we weigh, regulators in our brains try to keep us at our current body weight,” says Ariel Aspiras, also of Harvard Medical School. MC4R is one of those regulators.
MC4R mutations, including one that’s identical in cavefish and humans, are the most common single-gene cause of inherited obesity, according to Tabin. The mutation appears to reduce the gene’s activity, taking the brakes off what would otherwise be an appetite suppressor. Although the resulting uncontrolled eating can lead to obesity and illness in people, the mutation is advantageous for cavefish.
In the distant past, it may also have been good for humans. But that was then and this is now.
Long before today’s obesity epidemic, “people were on the heavier side,” says Rohner. “Knowing how these fish became fat might help us understand our species’ history. Many of us have to fight the desire to eat sweet and fatty things. Using these cavefish as a model system, we hope to find ways of resisting that urge.”
For now, it might be best to think twice about that double hot-fudge sundae with whipped cream. Unless, that is, you’re a blind cavefish.
In addition to Tabin, Aspiras and Rohner, other authors of the paper are Brian Martineau of Harvard Medical School and Richard Borowsky of New York University. The research was funded by the National Institutes of Health.
