A molecule found in the blood of pythons, which surges after the snakes consume large prey, has shown promise in inducing weight loss in obese mice, potentially opening a recent avenue for obesity drug development.
Researchers at Stanford University and the University of Colorado Boulder discovered that the metabolite, dubbed pTOS, is produced by gut bacteria in pythons and, while present in low levels in human urine, triggers significant appetite suppression when administered to mice. The findings, published in the journal Nature Metabolism, suggest a novel approach to weight management that differs from existing drugs like Wegovy.
Pythons are uniquely adapted to survive long periods without food, capable of consuming prey equivalent to their own body weight in a single meal and then fasting for up to 18 months. Scientists initially investigated the physiological changes that occur in pythons following a large meal, specifically focusing on the dramatic expansion of the heart – a 25% increase in size – and the 4,000-fold acceleration of metabolism required for digestion. The study involved examining blood samples from young Burmese pythons, weighing between 1.5kg and 2.5kg, before and after they were fed meals representing 25% of their body weight, following a 28-day fast.
The research team identified over 200 molecules that increased in the pythons’ blood after feeding, with pTOS exhibiting the most substantial rise – more than 1,000-fold. “We wondered whether this metabolite affected any of the post-feeding physiological changes in the snake,” explained Dr. Jonathan Long, an associate professor of pathology at Stanford University and co-author of the study.
Surprisingly, pTOS did not significantly impact energy expenditure or organ size in the mice. Instead, it demonstrably altered their eating behavior. Obese mice treated with pTOS consumed considerably less food than a control group and experienced a 9% reduction in body weight over 28 days.
This mechanism appears distinct from that of GLP-1 receptor agonists like Wegovy, which slow gastric emptying to promote feelings of fullness and can cause side effects such as nausea and constipation. PTOS, according to the research, acts on the hypothalamus, a region of the brain known to regulate appetite. “We’ve basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have,” said Prof. Leslie Leinwand, a biologist at the University of Colorado Boulder and a co-author of the research.
While acknowledging the need for further investigation before clinical application, researchers are optimistic about the potential for pTOS due to its natural presence in humans, suggesting a potentially favorable safety profile. “I have a healthy respect for snakes,” Leinwand added. “We can learn so much from these animals that have evolved to do extreme things.”
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