Pythons can stretch as long as a telephone pole and swallow an antelope or alligator whole. They are a wonder of nature. Consider what they feed on:
In the first 24 hours after devouring its huge prey, its heart grows by 25%, its cardiac tissue softens dramatically, and the organ compresses more and more, causing its heart rate to more than double. At the same time, a large number of specialized genes come into action, increasing the snake’s metabolism by forty-fold. Two weeks later, after its feast is digested, all systems return to normal – its heart is only slightly larger and even stronger than before.
This extraordinary process, described by CU Boulder researchers this week in the journal PNAScould ultimately inspire new treatments for a common human heart condition called cardiac fibrosis, in which heart tissue stiffens, as well as a host of other modern ailments that the monstrous snakes seem to miraculously resist.
“Pythons can go months or even a year without food in the wild, and then eat more food than they eat, and nothing bad happens to them,” said lead author Leslie Leinwand, a professor of molecular, cellular and developmental biology at CU Boulder and scientific director of the BioFrontiers Institute. “We think they have mechanisms to protect their hearts from things that would be harmful to humans. This study goes a long way toward identifying what those mechanisms are.”
What pythons and athletes have in common
Leinwand began studying pythons nearly two decades ago, and her lab remains one of the few in the world looking to these burrowing, nonvenomous reptiles for clues to improving human health.
Pythons can grow up to 6 metres long, depending on the species, and are typically found in resource-poor regions of Africa, South Asia and Australia. They fast for long periods of time, but when they do eat, they eat a lot.
“Most people who use animal models to study disease and health tend to focus on rats and mice, but you can learn a lot from animals like pythons that have evolved ways to survive in extreme environments,” said Leinwand, whose students travel to Oklahoma each year to purchase baby snakes from a breeder and raise them to adulthood in the Boulder lab.
There are two types of heart growth in humans, explains Leinwand: healthy, which occurs with chronic endurance training, and unhealthy, which occurs with disease.
Pythons, like top athletes, are characterized by healthy heart growth.
Their previous work has shown that over the course of about a week to ten days after a meal, pythons’ hearts grow significantly larger, their heart rate doubles, and their bloodstream turns a milky white color from circulating fats, which surprisingly nourishes rather than damages their heart tissue.
The new study should investigate how this all happens.
The researchers fed pythons that had fasted for 28 days a meal equal to 25% of their body weight and compared them to snakes that had not been fed.
They discovered that as the well-fed snakes’ hearts grew, special bundles of heart muscle called myofibrils – which help the heart expand and contract – radically softened and contracted with about 50% more force. At the same time, the same snakes had different metabolites in their blood and showed “profound epigenetic differences” – differences in which genes were turned on or off – than the fasted snakes.
“It is fascinating how pythons can alter their metabolism and contractile force, which is particularly relevant given the frequency of cardiac metabolic disorders in humans,” said lead author Claudia Crocini, a former postdoctoral fellow in Leinwand’s lab and now group leader at the German Heart Center Charité (DHZC) in Berlin.
Towards new treatments for metabolic diseases
Further research is needed to determine exactly which genes and metabolites play a role here and what they do. However, the study suggests that some genes stimulate the python heart to burn fat instead of sugar as an energy source. Diseased hearts in particular have difficulty doing this.
“We found that the python heart is fundamentally capable of radically remodeling itself, becoming much less stiff and much more energy efficient in just 24 hours,” said Leinwand. “If we could figure out how the python does this and use it for therapy in humans, that would be extraordinary.”
Stiff or fibrotic tissue leads to disease in organs other than the heart, such as the lungs and liver, so the findings could have applications there, too, says Leinwand, whose previous discoveries have helped lead to the development of several blockbuster drugs for heart disease.
Leinwand points out that unlike their counterparts in other parts of the world, pythons in the Florida Everglades have and use an endless supply of food, yet manage to remain physically and metabolically healthy. They may hold clues to how to prevent or reverse metabolic syndrome and other obesity-related diseases.
Your lab is also investigating this.
“The fact that they can eat endlessly without any real negative health consequences makes them ideal candidates for studies,” she said.
