Python blood could hold the secret to healthier weight loss
A metabolite found in the snakes quells appetite without causing stomach problems
image:
Pet pythons, belonging to graduate student Skip Maas, in the lab.
view moreCredit: Patrick Campbell/CU Boulder
University of Colorado Boulder researchers have discovered an appetite-suppressing compound in python blood that helps the snakes consume enormous meals and go months without eating yet remain metabolically healthy.
The research, a collaboration with scientists at Stanford and Baylor universities, could inform new weight loss therapies that promote satiety without the nausea and muscle loss that can come with existing drugs.
The findings appear in the journal Natural Metabolism on March 19.
“This is a perfect example of nature-inspired biology,” said senior author Leslie Leinwand, a distinguished professor of Molecular, Cellular and Developmental Biology who has been studying pythons in her lab for two decades. “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.”
Metabolic superpowers
Pythons can grow as big as a telephone pole, swallow an antelope whole, and go months or even years without eating — all while maintaining a healthy heart and plenty of muscle mass. In the hours after they eat, Leinwand’s research has shown, their heart expands 25% and their metabolism speeds up 4,000-fold to help them digest their meal.
To get a better sense of what makes these superpowers possible, Leinwand teamed up with Jonathan Long, an associate professor of pathology at Stanford University who studies metabolic byproducts in the blood, or metabolites, to learn how mammals take in and expend energy.
Long’s lab recently examined the blood of another curious creature— the racehorse — for insight on how the animals can endure those all-out sprints.
“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,” said Long.
For the new study, the team measured blood samples from ball pythons and Burmese pythons, fed once every 28 days, immediately after they ate a meal.
In all, they found 208 metabolites that increased significantly after the pythons ate. One molecule, called para-tyramine-O-sulfate (pTOS) soared 1,000-fold.
Further studies, done with Baylor University researchers, showed that when they gave high doses of pTOS to obese or lean mice, it acted on the hypothalamus, the appetite center of the brain, prompting weight loss without causing gastrointestinal problems, muscle loss or declines in energy.
The study found that pTOS, which is produced by the snake’s gut bacteria, is not present in mice naturally. It is present in human urine at low levels and does increase somewhat after a meal.
But because most research is done in mice or rats, pTOS has been overlooked.
“We’ve basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have,” said Leinwand, referring to drugs like Ozempic and Wegovy, which act on the hormone glucagon-like petide-1 (GLP-1).
Nature inspired biology
Leinwand noted that these new drugs were inspired by another reptile, the Gila monster. Gila monster venom contains a hormone similar to human GLP-1.
Those drugs are now used by millions, but studies show that as as many as half of people who use them stop taking them within a year.
“We believe there is still room for therapeutic growth in this market,” said Leinwand.
She, Long and her CU Boulder colleagues have formed a start-up, Arkana Therapeutics, to work toward commercializing some of the lessons they are learning from pythons.
They imagine a day when chemically synthesized analogs of the rare metabolites found in pythons could be turned into therapies to help people.
Weight loss isn’t the only therapeutic goal they are eyeing.
Age-related muscle loss, or sarcopenia, impacts nearly everyone to some degree as they get older, and people who have health problems that make it hard for them to exercise are hit particularly hard. To date, there are no therapies to halt or reverse sarcopenia.
The snakes may offer insight into how to do that, too, Leinwand said.
In future research, the team hopes to explore how pTOS works in people and catalogue the function of the other metabolites that increase after pythons eat. Some metabolites the researchers identified in their study soar by 500 to 800%.
“We’re not stopping with just this one metabolite,” said Leinwand. “There’s a lot more to be learned.”
Skip Maas, a PhD candidate in the Department of Molecular, Cellular and Developmental Biology, holds his personal pet snakes, Gaius and Agrippina. In the lab, Maas studies python metabolism to better understand how the snakes can eat so much, and go so long without eating, while remaining healthy.
Credit
Patrick Campbell/CU Boulder
Skip Maas (Right), graduate student in Molecular, Cellular, and Developmental Biology, and Leslie Leinwand, Distinguished Professor, Department of Molecular, Cellular, and Developmental Biology, observe Maas's two pet pythons Gaius and Agrippina. In addition to keeping pythons as pets at home, Maas studies python metabolism in Leinwand's lab. Photo by Patrick Campbell/University of Colorado
Credit
Patrick Campbell/CU Boulder
Journal
Nature Metabolism
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Python metabolomics uncovers a conserved postprandial metabolite and gut–brain feeding pathway
Article Publication Date
19-Mar-2026
COI Statement
A provisional patent application has been filed by Stanford University on para-tyramine- O-sulfate for the treatment of cardiometabolic diseases.
Pythons’ feast-and-famine life hints at new weight-loss pathway
A Pandora’s box of python proteins
Stanford Medicine
Pythons don’t nibble. They chomp, squeeze and swallow their prey whole in a meal that can approach 100% of their body weight. But even as they slither stealthily around the forest, months or even a year may pass between massive mouthfuls. This pattern of extreme feasting and fasting taxes their metabolism far beyond what humans experience on a day-to-day basis.
Now researchers at Stanford Medicine and the University of Colorado, Boulder, have found that a metabolite that spikes a thousandfold in pythons after a large meal causes obese laboratory mice to shun their food pellets and lose weight — mimicking the effect of semaglutide drugs such as Ozempic and Wegovy.
Although it’s too soon to tell whether this metabolite, called pTOS, will translate to a new weight loss drug in humans, the study solidifies the power of studying extremes in the animal kingdom. Reptiles have repeatedly gifted humans with clinically significant drugs. Snake venom is chockful of biologically active compounds that have been developed into blood pressure medications and anticoagulants. And semaglutide arose from the discovery of a hormone in the Gila monster that regulates blood sugar levels.
“Mammals have a relatively narrow physiologic and metabolic range,” said Jonathan Long, PhD, associate professor of pathology and a member of the Wu Tsai Neurosciences Institute. “Humans, for example, eat around 1% to 2% of their body weight each meal, and we eat about three times a day,” unlike snakes, who eat rarely and whose physiology changes drastically after a meal. “Obviously, we are not snakes. But maybe by studying these animals we can identify molecules or metabolic pathways that also affect human metabolism.”
Long is the senior author of the study, which will be published on March 19 in Nature Metabolism. Postdoctoral scholar Shuke Xiao, PhD; Mengjie Wang, MD, PhD, a postdoctoral scholar at the University of South Florida; and Thomas Martin, PhD, a postdoctoral scholar at the University of Colorado, Boulder, are the lead authors of the research.
Not exactly lab mice
Pythons aren’t common lab animals. They can weigh up to 200 pounds and live more than 20 years in the wild — a far cry from dainty laboratory mice. But their dramatic physiological response to sudden, large meals has drawn the attention of researchers. Within hours after eating, the pythons’ organs, including their hearts, begin to expand in size by 50% or more; their energy demands increase — digestion takes calories! — by more than 40%; and cells that don’t normally divide, like the insulin-producing beta cells in the pancreas, explode in number.
Researchers studying cardiac disease at the University of Colorado, Boulder, were interested in the sudden growth of the heart in pythons after feeding when they stumbled upon the metabolite. They examined blood from young Burmese pythons, weighing about 3.3 to 5.5 pounds, before and after a meal consisting of about 25% of their body weight. In the wild, Burmese pythons can go 12 to 18 months without eating; the laboratory snakes had fasted for 28 days prior to feeding. They also conducted similar tests in Ball pythons — a smaller relative of the Burmese python.
The scientists identified more than 200 molecules called metabolites that increased in abundance at least 32-fold in the pythons’ blood within hours after eating, and 24 that decreased by an equal margin. One increased more than a thousandfold — a dramatic meal-induced spike. The molecule, which the researchers subsequently identified as pTOS, is a little-studied metabolite in humans and is mainly known as a molecule excreted in urine.
“We wondered whether this metabolite affected any of the post-feeding physiological changes in the snake,” Long said. “But when we administered pTOS to laboratory mice at levels similar to what we saw in the pythons after eating, we didn’t see any effect on energy expenditure, beta cell proliferation or organ size. What it did regulate was the appetite and feeding behaviors of the mice.”
The researchers found that obese mice given pTOS ate significantly less than control mice and, after 28 days, had lost 9% of their body weight when compared with control animals. The newly svelte mice showed no changes in water intake, energy expenditure or movement throughout the treatment. Additional experiments showed that the effect of pTOS is not due to changes in hormones known to regulate feeding or to a reduction in the rate of stomach emptying, which is one way common GLP-1 medications like Ozempic reduce appetite.
Further experiments determined that pTOS is a byproduct of the breakdown of tyrosine — an amino acid present in dietary protein — by bacteria in the gut. Treating the pythons with antibiotics prior to feeding abolished the eating-associated increase in pTOS levels.
“We were able to work out a pathway in which pTOS is produced after a meal through the metabolism of tyrosine in the gut and the liver,” Long said. “We also found that it then goes to a region of the brain called the hypothalamus, which is a well-known regulator of energy homeostasis. There it activates neurons involved in regulating feeding behaviors.”
The metabolite in humans
The researchers then studied six publicly available datasets of blood from healthy volunteers before and after a meal. In five of the six, pTOS levels were elevated after eating, but only by about two- to fivefold. Such a small increase in humans would be extremely difficult to pick out among many other feeding-associated metabolic changes — illustrating the value of using pythons as a model animal.
But a few people were more snakelike than others. One individual in the databases experienced a more than 25-fold increase in pTOS after a meal, reaching python-level concentrations in their blood. (Because these datasets were from previously conducted studies, it is not possible to know whether this person felt more full or ate less than other study participants.)
Although more research needs to be conducted into the possible use of pTOS in humans to curb appetite, the pythons gave the researchers a plethora of additional molecules to study.
“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 and his colleagues speculate that, like blood pressure medications and anticoagulants, some of these molecules could be clinically useful. “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 remodeling,” Long said.
He noted that there’s an interest among scientists in augmenting human capabilities, such as creating vaccines that enhance the immune response. “Maybe this concept of using molecules first identified in snakes or other animals can extend to many other aspects of human health,” he said.
“We’re excited to learn from these snakes and other ‘extreme’ animals to inspire future discoveries,” he added.
The study was funded by the National Institutes of Health (grants R01GM029090, R01DK138518, R01DK105203, R01DK124265, K99DK141966, K99AR081618, F32HD112123, F32HL170637, F32DK138685 and T32GM142607), 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.
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About Stanford Medicine
Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu.
Journal
Nature Metabolism
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Python metabolomics uncovers a conserved postprandial metabolite and gut–brain feeding pathway
Article Publication Date
19-Mar-2026
