Binge-Eating Fish Living in Caves Provide Insight Into Human Obesity Genetics

fat fish
Mexican cave fish are known for their binge-eating habits, a result of evolutionary changes that have allowed them to adapt to an environment where food is scarce. Stephanie Dutchen

Geneticists at Harvard Medical School have discovered that a certain type of cave-dwelling fish, known for its binge-eating habits, has the same genetic mutation found in a small population of severely overweight people. Researchers have already identified variations to the MC4R gene in some individuals who are prone to compulsive overeating and are obese.

The findings, published this week in the Proceedings of the National Academy of Science, identify evolutionary changes to metabolic processes in fish that offer insight into why some people may be more genetically predisposed to obesity.

There are two different types of Astyanax mexicanus, a type of fish that lives in northeastern Mexico. Some Mexican cave fish live in surface waters out in the open, while others live in dark caves. The cave-dwellers have adapted in many ways to their setting. They've lost their eyes and pigmentation over time because of lack of light, and they have developed a resistance to starvation. The researchers say cave fish can live for months without any food by storing fat and burning calories at a slower rate than their cousins.

"The good news is no one wants to eat you in the caves because there's no predators. But the bad news is there's nothing to eat," says Clifford Tabin, the George Jacob and Jacqueline Hazel Leder professor of genetics and chair of the department of genetics at Harvard Medical School. Tabin led the team of graduate and doctoral students in their research.

These fish are so efficient at holding on to their fat that after two months without food, they lost only half as much weight as their cousins. After three months, the cave fish were still going strong, but the fish that didn't live in caves began to die.

The researchers say cave fish have evolved to become efficient overeaters with appetites to match in order to compensate for periods of time when there isn't food available in their natural habitat. It sounds like hibernating, except these fish don't actually sleep through periods of famine.

"Cave fish are constantly circling and searching for food," says Tabin. "They're in fact more active than river fish."

Their ability to stay healthy and fat is partially attributed to the MC4R gene, which regulates leptin, a functional hormone that's responsible for appetite suppression. The gene is also involved in regulating insulin in the brain.

Previous research has already identified this biomarker in obese individuals. One study found mutations in the MC4R gene exist in approximately 1 to 2.5 percent of people with a body mass index greater than 30, a clinical measure of obesity. According to that study, leptin deficiency caused by certain mutations to the MC4R gene is the most common obesity syndrome and one of the most common genetic diseases, with an even higher prevalence than conditions such as cystic fibrosis.

From an evolutionary standpoint, mutations to the MC4R gene may have once served humans well. But these days, in the developed world, food scarcity is less of a problem, which means mutations to the MC4R gene can be a roadblock for achieving and maintaining a healthy weight for some people. "Everyone has a friend who eats a lot and never gains weight, and others who touch a doughnut and gain 5 pounds," says Tabin.

The researchers believe that most likely there are other genes involved in the metabolism of cave fish. The group hopes to identify gene mutations that could explain why the fish have fatty livers or an increased appetite. This could provide information on which genes may be worthwhile to study in humans to gain a clearer understanding of hereditary obesity.