Pythons follow the ultimate crash diet, swallowing an antelope in a single sitting and then going for months without eating. Now scientists have identified a molecule that appears to be crucial for this metabolic feat, and which they say could pave the way for a new class of obesity drugs.
When the python metabolite, which spikes in their blood after eating, was given to obese mice, they shunned food and rapidly lost weight. The scientists said the molecule could have a similar effect to drugs such as Wegovy.
“Obviously, we are not snakes,” said Dr Jonathan Long, an associate professor of pathology at Stanford University and co-author of the research. “But maybe by studying these animals, we can identify molecules or metabolic pathways that also affect human metabolism.”
Burmese pythons can grow to more than 5 metres (16ft) in length and close to 100kg (220lbs) in weight. In the wild, the snakes consume prey that can approach 100% of their body weight. In the hours after a python eats, its heart expands by 25% and its metabolism speeds up 4,000-fold to help it digest the meal. They can then go for 12 to 18 months without eating, seemingly with few ill effects.
Initially, the scientists had set out to uncover the metabolites involved in pythons’ sudden heart growth after feeding. They examined blood from young Burmese pythons, weighing about 1.5kg to 2.5kg, before and after a meal consisting of about 25% of their body weight. The laboratory snakes had fasted for 28 days before feeding.
The scientists identified more than 200 molecules that significantly increased in the pythons’ blood within hours after eating, and one that increased more than 1,000-fold. This molecule, called pTOS, is produced by the snake’s gut bacteria and is also known to be present at low levels in human urine. Long said: “We wondered whether this metabolite affected any of the post-feeding physiological changes in the snake.”
However, when pTOS was administered to laboratory mice, there were no obvious effects on energy expenditure or organ size. “What it did regulate was the appetite and feeding behaviours of the mice,” Long added.
Obese mice given pTOS ate significantly less than control mice and, after 28 days, had lost 9% of their body weight.
The molecule appeared to work in a different way to GLP-1 medications such as Wegovy, which partly work by slowing down stomach-emptying, which in turn makes people feel full for longer but is also linked to nausea, constipation and stomach pain. Instead, pTOS appears to act on a brain region, the hypothalamus, which is known to regulate appetite.
Prof Leslie Leinwand, a biologist at the University of Colorado Boulder who has been studying pythons for two decades and was a co-author of the research, said: “We’ve basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have.”
Leinwand said further research would be needed before the findings could be applied clinically, but that since pTOS occurred naturally in humans, it would be expected to be safe. “I have a healthy respect for snakes,” Leinwand added. “We can learn so much from these animals that have evolved to do extreme things.”
The findings are published in the journal Nature Metabolism.
