The search for recent obesity treatments may have taken an unlikely turn, inspired by the remarkable metabolic feats of Burmese pythons. Scientists have identified a molecule, dubbed pTOS, found in the blood of these snakes, that dramatically suppresses appetite in mice, leading to significant weight loss. The discovery, published Thursday in the journal Nature Metabolism, offers a potential pathway to developing a new class of weight loss drugs with fewer side effects than current options.
Pythons are known for their ability to consume prey weighing up to 100% of their own body weight in a single sitting, then endure months without another meal. This extreme physiology requires a unique metabolic strategy, and researchers at Stanford University and the University of Colorado Boulder sought to understand the underlying mechanisms. Their investigation focused on the dramatic changes pythons undergo after feeding, particularly the 4,000-fold increase in metabolism and the 25% expansion of the heart.
The team examined blood samples from young Burmese pythons, weighing between 1.5 and 2.5 kilograms, before and after they were fed a meal representing about 25% of their body weight, following a 28-day fast. They identified over 200 molecules that increased significantly in the snakes’ blood within hours of eating, with pTOS standing out due to a more than 1,000-fold increase. PTOS is produced by gut bacteria in the python and is as well present, albeit in low levels, in human urine, raising the possibility of its safe application in humans.
How pTOS Impacts Appetite
Initial experiments focused on understanding how pTOS affected the physiological changes observed in pythons. However, when administered to obese mice, the molecule didn’t significantly alter energy expenditure or organ size. Instead, researchers, including Dr. Jonathan Long, an associate professor of pathology at Stanford University, found that pTOS powerfully regulated appetite and feeding behavior. “What it did regulate was the appetite and feeding behaviours of the mice,” Long said.
Obese mice receiving pTOS consistently ate less than control groups, resulting in a 9% reduction in body weight over 28 days. This effect is particularly noteworthy because it appears to operate through a different mechanism than existing GLP-1 medications like Wegovy, which work by slowing stomach emptying to promote feelings of fullness. GLP-1 drugs, even as effective, can cause side effects such as nausea, constipation, and stomach pain.
Instead, pTOS appears to target the hypothalamus, a region of the brain central to regulating appetite. This suggests a potentially more direct approach to controlling hunger without the gastrointestinal side effects associated with current medications. The discovery is a prime example of “nature-inspired biology,” according to Prof. Leslie Leinwand, a biologist at the University of Colorado Boulder and a co-author of the study.
A Natural Appetite Suppressant?
Leinwand, who has studied pythons for two decades, explained that the research team essentially uncovered an appetite suppressant that, in mice, avoids some of the drawbacks of GLP-1 drugs. “We’ve basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have,” she said. Leinwand has a track record of translating animal research into clinical applications, having previously co-founded two companies that were acquired by pharmaceutical firms for billions of dollars.
The fact that pTOS occurs naturally in humans is encouraging, Leinwand added, suggesting it may be well-tolerated. However, she emphasized that extensive further research is needed before the findings can be translated into clinical treatments. The team is now focused on understanding the precise mechanisms by which pTOS interacts with the hypothalamus and whether similar effects can be replicated in humans.
Looking Ahead
The potential implications of this research extend beyond obesity treatment. Understanding how pythons regulate their metabolism could also provide insights into other metabolic disorders and age-related conditions. As Leinwand noted, “We can learn so much from these animals that have evolved to do extreme things.”
The next steps involve rigorous testing to determine the safety and efficacy of pTOS in larger animal models and, eventually, in human clinical trials. While the path from laboratory discovery to approved medication is long and complex, the initial findings offer a promising new avenue for addressing the global obesity epidemic. Researchers will also be investigating the specific gut bacteria responsible for producing pTOS, potentially opening the door to probiotic-based interventions.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
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