"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," he added. Understanding how these fish became fat might eventually help us understand how we did." "There was selection for that in our evolution, but we don't know why. Even before the modern obesity epidemic, humans as a species were, relatively speaking, "very fat," Rohner pointed out. Once upon a time, it might have been advantageous for humans, too. Although this can be disastrous for people-children with MC4R mutations can't stop eating-it has proven advantageous for the fish. Rohner and Aspiras found that the mutations appear to reduce the gene's activity in the cavefish, taking the brakes off their appetite suppressor.
In people, MC4R mutations-including one that is identical in some of the cavefish-are the most common single-gene cause of inherited obesity. Lab mice without MC4R are severely obese and constantly hungry. "When people try to diet or change how much they weigh, there are regulators in your brain that try to keep you at your current body weight. "It's one of the key components in maintaining your energy balance," explained Aspiras. Most of the cavefish had mutations in MC4R, a gene known to be regulated by leptin (an appetite-suppressing hormone) and insulin in the human brain.
The research team analyzed the DNA of fish from several different caves as well as from the surrounding surface rivers to find out what genetic mutations could be driving the differences in metabolism, body weight and appetite. The team wants to investigate how this happens with the hope that it could one day help people living with obesity. Remarkably, the cavefish live long, healthy lives despite being so overweight. Of course, he added, "studying hibernating bears is harder than studying fish." How did the cavefish become so obese in the first place?įurther investigation revealed that some cave populations evolved to have insatiable appetites so that when food does become available, swept in by floods perhaps once a year, the fish are able to eat without limit and store as much fat as they can to sustain them until the next feast.Īlthough the cavefish don't sleep through times of scarcity, "this model could be similar to hibernating animals in that they live off stored fat for extended periods," said Rohner. "We think the cavefish can go much longer than that, due to their immense fat reserves," said Rohner.
After three months, the cavefish were "totally fine," while the surface fish began to die. Rohner and co-first author Ariel Aspiras, a graduate student in the Tabin lab, found in lab experiments that after two months without food, the cavefish lost half as much weight as surface populations. "And although they are active, their metabolism is slower." "These fish are very, very fat-much fatter than surface fish," said Nicolas Rohner, a postdoctoral researcher in the Tabin lab and co-first author of the study. The cavefish withstand months without sustenance by storing massive amounts of fat and burning it more slowly. With little food, they became resistant to starvation. Without light, they gradually lost their eyes and pigmentation. In the hundreds of thousands of years since they were separated from their surface-dwelling cousins, they have adapted to their harsh environment in several ways. "Some of the mechanisms we see in the fish may well have implications for human metabolism and therefore human health."Īs the name suggests, Mexican cavefish live in dark, isolated caves in northeastern Mexico. "The work with the cavefish gives us an example in a natural setting of why and how metabolisms evolved to be different," he said. "We all know that people have different metabolisms that lead to their gaining weight under different amounts of eating," said the study's senior author, Clifford Tabin, the George Jacob and Jacqueline Hazel Leder Professor of Genetics and chair of the Department of Genetics at HMS. The findings, published in PNAS, reveal more about how vertebrates evolved to have different metabolisms from one another and could provide insights into the relationship between human obesity and disease.
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