Blind cavefish are very fat and remarkably starvation resistant, which is really useful as they live in dark, nutrient-poor environments. Once a year or so, when food is swept in by floods, they binge eat. Now, researchers studying how cavefish survive when food is scarce have identified the genetic changes behind their metabolic adaptations. The findings, published in Proceedings of the National Academy of Sciences, may help researchers to better understand human obesity.
"We all know that people have different metabolisms that lead to their gaining weight under different amounts of eating," Harvard’s Clifford Tabin says in a statement. "The work with the cavefish gives us an example in a natural setting of why and how metabolisms evolved to be different."
In obscure, remote caves, photosynthesis is nonexistent, and the only sources of nutrition are decaying animals, bat droppings, and detritus from seasonal floods. To withstand months without sustenance, cavefish rely on large reserves of body fat and a slow-burning metabolism. And even though they’re constantly hungry, they lead healthy lives.
To understand the genetic underpinnings of these adaptations, Tabin’s team compared Mexican cavefish (Astyanax mexicanus) who dwell in caves to those who live in surface rivers. The two populations separated hundreds of thousands of years ago, and the ones who live without light have lost their eyes and pigmentation. "These fish are very, very fat – much fatter than surface fish," co-first author Nicolas Rohner of Harvard says. "And although they are active, their metabolism is slower." They’re not unlike hibernating bears.
Compared to surface-dwellers, the insatiable cave-dwellers display a larger appetite and more triglyceride fats with regular feeding. After two months of fasting, the cave-dwellers lost half as much body weight as surface-dwellers. Even after three months, when the surface fish began to starve, the blind cavefish were fine. "We think the cavefish can go much longer than that, due to their immense fat reserves," Rohner adds.
When the team analyzed the genome sequences of the cave-dwelling fish, they found mutations in the melanocortin 4 receptor (MC4R) gene, which has been linked to anorexia in humans. The receptor is regulated by insulin and an appetite-suppressing hormone, and it is likely to play a role in overfeeding. "It's one of the key components in maintaining your energy balance," lead author Ariel Aspiras of Harvard explains. "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. MC4R is one of them."
Having replaced the amino acid glycine with serine in MC4R, the cavefish showed reduced gene activity: This basically suppresses their appetite suppressor, allowing them to eat without limit. While other genes are certainly involved, the team thinks that this receptor is a strong candidate for natural selection in cavefish. That same MC4R mutation is the most common single-gene cause of inherited obesity in people.
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