A blind cave-dwelling fish that ekes out a meagre existence on bat droppings has helped scientists tackle a medical paradox: how prolonged starvation can cause people to develop a fat-filled liver, which is usually associated with obesity. The finding could give insights into the mechanisms of how malnutrition damages our bodies.
The liver has long been known to be harmed in a kind of malnutrition called kwashiorkor, which features severe protein deficiency. Droplets of fat accumulate in its cells, damaging them and causing the organ to waste away.
The condition is also seen in many starving animals. But now at the Université Libre de Bruxelles in Belgium and his colleagues have discovered an intriguing exception: the Mexican tetra fish (Astyanax mexicanus). This species comes in two kinds – a cave-dwelling population, which endures periods of starvation, and a surface-dwelling population, which doesn’t.
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Having discovered that starving cave fish larvae don’t get fatty livers, the researchers compared gene activity in the larvae of cave tetra, surface tetra and zebrafish while they were fasting and while they were fed. They identified a gene for a protein that transports fat molecules called fatty acids into cells. This gene’s activity increased in starving surface tetra and zebrafish larvae, but not in starving cave fish larvae.
When starving zebrafish larvae were given a drug that blocks the activity of the protein, they experienced much less fat accumulation and wasting in their livers. Further experiments showed that a similar mechanism exists in fruit flies, suggesting this starvation response is at least 400 million years old.
Until now, most research into the mechanisms of malnutrition has been done in cells in a lab dish, says Singh. In the tetra, evolution has provided an opportunity to explore them in whole animals. “It’s really a whole-body response,” says Singh. “I think that such systems will be better at answering those questions.”
A drug that modifies the starvation response in humans could find uses in high-income countries, but this is a long way off, says Singh. Meanwhile, the team plans to investigate applications in domesticated animals like cats, which are prone to getting fatty livers if they lose their appetites.
Scientifically, the findings are “hugely interesting”, says , a public health specialist at the London School of Hygiene & Tropical Medicine. “I think it does inspire wonder in the natural world and how many lessons there are that we can learn from these different adaptations.”
But he adds that there are already well-established approaches to treating malnutrition in countries with high levels of poverty and that the main challenges lie in implementing them. “It is a medical emergency in its most severe form,” says Kerac. “But we also don’t want to have the impression that it’s purely medical, when fundamentally it’s a social and economic issue.”
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