Obesity drugs like Wegovy and Mounjaro are wildly popular, but some people avoid taking them for fear of side effects such as nausea, abdominal pain, or muscle loss. Then what if there were an obesity drug that lets you binge once and fast for months while staying healthy without any side effects? U.S. scientists have found a candidate for a dream obesity treatment in pythons that binge and then fast for long periods.
A team led by Leslie Leinwand of the University of Colorado's Department of Molecular, Cellular and Developmental Biology said on the 20th in the journal Nature Metabolism that it "found an appetite-suppressing compound in python blood that allows them to stay healthy even after consuming a massive amount of food and then not eating for months." The team demonstrated the appetite-suppressing effect by administering components of python blood to mice.
Burmese pythons grow longer than 5 meters and weigh close to 100 kilograms. In the wild, pythons swallow prey whole, eating as much as their body weight in one go. According to Leinwand, who has studied pythons for 20 years, after a single binge, a python's heart expands 25% for several hours and its metabolism speeds up 4,000-fold to aid digestion. It then eats nothing for 12 to 18 months while remaining healthy.
◇In obese mice, body weight down 9% in 28 days
Leinwand and Jonathan Long of Stanford University School of Medicine tracked substances in python blood that underpin their extreme fasting ability. Long had previously identified a substance in racehorse blood that helps them endure intense sprints. Young lab-raised pythons weighed 1.5 to 2.5 kilograms. They fasted for 28 days and then ate a single meal equal to 25% of their body weight. The researchers drew blood before and after the binge and analyzed its components.
The team identified more than 200 components whose concentrations in blood rose sharply within hours after pythons ate. Among them, para-tyramine-O-sulphate (pTOS) increased more than 1,000-fold. This compound is tyramine, derived from the amino acid tyrosine, conjugated with a sulfate group. pTOS is produced by gut bacteria in snakes and is known to be present in trace amounts in human urine.
When python-derived pTOS was given to obese mice, their food intake decreased and body weight fell by 9% after 28 days. It delivered effects similar to glucagon-like peptide-1 (GLP-1) obesity drugs such as Wegovy and Mounjaro. GLP-1 is a hormone secreted by the small intestine after meals. It promotes insulin secretion in the pancreas to lower blood sugar and suppresses glucagon, which raises blood sugar. Drugs that mimic this were originally developed as diabetes treatments to reduce blood sugar and later evolved into obesity drugs after their weight-loss effects were confirmed.
GLP-1 obesity drugs reduce appetite in the brain while slowing the rate at which food leaves the stomach, increasing fullness and reducing weight. By contrast, pTOS did not affect mice's energy expenditure or organ size. The only change was appetite. Co–corresponding author Yong Xu of Baylor College of Medicine said the pTOS given to mice acted on the hypothalamus, the brain's appetite-control center, inducing weight loss without causing gastrointestinal problems, muscle loss, or reduced energy.
◇No muscle loss, no digestive side effects
Leinwand said it was "a discovery of a new appetite suppressant without the side effects seen with GLP-1 drugs." Because GLP-1 obesity drugs slow gastrointestinal emptying, they can sometimes cause side effects such as nausea, constipation, or abdominal pain. By contrast, the python blood component suppresses only appetite, so those side effects do not appear, the researchers said. The fact that pythons remain healthy after bingeing and then fasting long-term can be seen as evidence of that effect.
Although pTOS is detected in trace amounts in human urine, it does not appear in mice. Because mice and rats have been used as laboratory stand-ins for humans, the effect of pTOS has been overlooked, the team said. "To fully understand metabolism, we have to go beyond observing mice or humans and look at the most extreme metabolic phenomena that nature offers," Long said.
Leinwand noted that "more research is needed before these findings can be applied to humans, but because pTOS is a substance that is produced naturally in humans, it is expected to be safe," adding that the team was inspired by the fact that a diabetes treatment came from the Gila monster, a fellow reptile.
Eli Lilly and Company and Amylin Pharmaceuticals in the United States developed exenatide, the world's first GLP-1 diabetes treatment, in 1992 based on a substance extracted from Gila monster venom. The drug later became the foundation for the development of GLP-1 diabetes and obesity treatments.
Leinwand and Long founded the startup Arkana Therapeutics to commercialize python blood components as a therapy. The researchers said that because the python blood component reduced body weight without causing muscle loss, it could treat not only obesity but also muscle loss due to aging or disease.
References
Nature Metabolism (2026), DOI: https://doi.org/10.1038/s42255-026-01485-0