Scientists studying the extraordinary metabolism of Burmese pythons have identified a python blood molecule that dramatically suppresses appetite in obese mice, raising the prospect of a new class of weight loss therapies that could avoid some of the side effects associated with existing drugs such as Ozempic and Wegovy.
The research, published on 19 March 2026 in the journal Nature Metabolism, was led by teams at Stanford University, the University of Colorado Boulder and Baylor University. The scientists found that a metabolite called para-tyramine-O-sulfate, or pTOS, surges more than 1,000-fold in pythons’ blood within hours of eating. When administered to obese laboratory mice, the molecule caused the animals to eat significantly less, leading to a 9% loss of body weight over 28 days, without the gastrointestinal problems, muscle loss or declines in energy expenditure that can accompany current GLP-1 medications.
The findings offer a striking example of how studying animals with extreme physiological capabilities can yield insights with potential relevance to human medicine.
The metabolic superpowers of pythons
Burmese pythons are among nature’s most remarkable metabolic performers. The snakes can grow to more than five metres in length and weigh close to 100 kilograms. In the wild, they consume prey that can approach 100% of their own body weight, swallowing it whole in a single sitting. In the hours after a meal, their hearts expand by approximately 25%, their metabolism accelerates by up to 4,000-fold to support digestion, and cells that do not normally divide, including insulin-producing beta cells in the pancreas, undergo rapid proliferation. Between meals, the snakes can go 12 to 18 months without eating, apparently suffering few ill effects.
It was this capacity for extreme feasting and fasting that drew the attention of Professor Leslie Leinwand, a distinguished professor of molecular, cellular and developmental biology at the University of Colorado Boulder, who has been studying pythons in her laboratory for two decades. Leinwand’s group had initially set out to investigate the sudden enlargement of the python heart after feeding, seeking insights that might be applicable to cardiac disease research.
“This is a perfect example of nature-inspired biology,” Leinwand said. “You look at extraordinary animals that can do things that you and I and other mammals can’t do, and you try to harness that for therapeutic interventions.”
Discovering pTOS
To explore the metabolic changes triggered by feeding, Leinwand teamed up with Dr Jonathan Long, an associate professor of pathology at Stanford University and a member of the Wu Tsai Neurosciences Institute, who studies metabolic byproducts in the blood to understand how mammals take in and expend energy.
“If we truly want to understand metabolism, we need to go beyond looking at mice and people and look at the greatest metabolic extremes nature has to offer,” Long said.
The team examined blood samples from young Burmese pythons, weighing between approximately 1.5 and 2.5 kilograms, before and after a meal consisting of around 25% of the animals’ body weight. The laboratory snakes had fasted for 28 days prior to feeding. Similar tests were also conducted in ball pythons, a smaller relative.
In total, the scientists identified more than 200 metabolites that increased significantly in the pythons’ blood within hours of eating, and 24 that decreased by a comparable margin. One molecule stood out above all others: pTOS, which increased more than 1,000-fold, a dramatic spike unmatched by any other metabolite in the dataset. The python blood molecule was produced by gut bacteria as a byproduct of tyrosine breakdown.
Further investigation revealed that pTOS is produced by bacteria in the snake’s gut as a byproduct of the breakdown of tyrosine, an amino acid found in dietary protein. The molecule is also known to be present at low levels in human urine and has been detected in human blood at modestly elevated concentrations after meals, though the increases in humans are far smaller, typically in the range of two to fivefold.
“We wondered whether this metabolite affected any of the post-feeding physiological changes in the snake,” Long said.
How pTOS works in mice
When the researchers administered this python blood molecule to laboratory mice at levels comparable to those observed in pythons after eating, there were no obvious effects on energy expenditure, organ size or beta cell proliferation. What did change was the animals’ appetite.
Obese mice given pTOS ate significantly less than untreated control animals and, after 28 days, had lost 9% of their body weight by comparison. The treated mice showed no changes in water intake, energy expenditure or physical activity throughout the treatment period. Crucially, pTOS did not appear to cause the nausea, constipation or stomach pain that are common side effects of GLP-1 receptor agonist drugs such as Wegovy, which partly work by slowing the rate at which the stomach empties.
Instead, additional experiments revealed that pTOS acts on the hypothalamus, the region of the brain known to regulate appetite and energy balance. There, it activates neurons involved in controlling feeding behaviour, suppressing the urge to eat through a mechanism distinct from that of existing weight loss medications.
“We’ve basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have,” Leinwand said.
Lessons from reptiles
The discovery of pTOS adds to a growing list of clinically significant compounds derived from reptiles. Snake venom has yielded biologically active molecules that have been developed into blood pressure medications and anticoagulants. Semaglutide, the active ingredient in Ozempic and Wegovy, was itself inspired by a hormone found in the venom of the Gila monster, a venomous lizard native to the southwestern United States, which regulates blood sugar levels in a manner similar to human GLP-1.
GLP-1 drugs are now used by millions of people worldwide, but studies suggest that as many as half of those prescribed such medications stop taking them within a year, often due to gastrointestinal side effects. The researchers believe there remains significant scope for new therapies that achieve similar weight loss outcomes through different biological pathways.
“We believe there is still room for therapeutic growth in this market,” Leinwand said.
Long echoed the sentiment, noting that while the current findings are limited to mice, the principle of drawing on nature’s extremes has a strong track record. “Obviously, we are not snakes,” he said. “But maybe by studying these animals, we can identify molecules or metabolic pathways that also affect human metabolism.”
From pythons to patients
While the researchers stressed that considerably more work is needed before this python blood molecule could be considered for clinical use in humans, the early signs are encouraging. The fact that the molecule occurs naturally in human urine suggests it may be tolerated by the human body, although its effects on human appetite and metabolism have yet to be tested directly.
Among the datasets of human blood samples the team examined, most individuals showed modest post-meal increases in pTOS. However, one participant experienced a more than 25-fold spike after eating, reaching concentrations comparable to those seen in pythons. Because the data came from previously conducted studies, it was not possible to determine whether this individual felt fuller or ate less than other participants.
Leinwand, Long and colleagues at the University of Colorado Boulder have formed a startup company, Arkana Therapeutics, to explore the commercial potential of their python-derived discoveries. The team envisions a future in which chemically synthesised analogues of the rare metabolites found in pythons could be developed into therapies for obesity and other conditions.
Weight loss is not the only therapeutic goal under investigation. Age-related muscle loss, or sarcopenia, affects nearly everyone to some degree as they grow older, and there are currently no approved therapies to halt or reverse its progression. The pythons’ ability to maintain healthy muscle mass during prolonged periods without food may offer valuable clues.
“We’re not stopping with just this one metabolite,” Leinwand said. “There’s a lot more to be learned.”
A broader landscape of discovery
The study identified more than 200 metabolites that change significantly in pythons after feeding, many of which remain poorly understood. Some increased by 500 to 800%, and the researchers noted that several resemble hormones but have no known equivalent in mice or humans.
“We’re generating a landscape of molecules that vary in prevalence after eating in all organs of these snakes,” Long said. “We already found many that look like hormones but that have no similarity with any known hormones in mice or humans. This is a form of natural product discovery.”
Long speculated that some of these molecules could eventually prove as clinically useful as the reptile-derived compounds that came before them, from blood pressure drugs to the GLP-1 agonists reshaping the treatment of obesity and diabetes. “Maybe a patient with Type 1 diabetes due to defective beta cell function could benefit from a snake molecule that stimulates cell division, or a person with liver disease could take a snake-derived drug that facilitates organ remodelling,” he said.
The research was funded by the National Institutes of Health, the Wu Tsai Human Performance Alliance, the Stanford Diabetes Research Center, the Phil and Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, the Ono Pharma Foundation, the Leducq Foundation, the American Heart Association, and the Stanford University Medical Scientist Training Program.
