University of Colorado Boulder researchers announced on March 19 the discovery of an appetite-suppressing compound in python blood that enables the snakes to consume large meals and go months without eating while remaining metabolically healthy.
The research, conducted with scientists from Stanford and Baylor universities, could lead to new weight loss treatments that promote feelings of fullness without causing nausea or muscle loss, which are side effects sometimes seen with current medications. The findings were published in the journal Natural Metabolism.
"This is a perfect example of nature-inspired biology," said Leslie Leinwand, senior author and distinguished professor of Molecular, Cellular and Developmental Biology. "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."
Pythons are known for their ability to grow very large, swallow prey whole, and survive long periods without food while maintaining heart health and muscle mass. After eating, their heart size increases by 25% and metabolism speeds up dramatically. To understand these abilities, Leinwand collaborated with Jonathan Long from Stanford University, who studies metabolic byproducts in blood. Long said: "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."
The team measured blood samples from ball pythons and Burmese pythons after feeding them once every 28 days. They identified 208 metabolites that increased after eating; one molecule called para-tyramine-O-sulfate (pTOS) rose by 1,000 times. Further studies showed that giving high doses of pTOS to mice led to weight loss without gastrointestinal issues or muscle loss.
Leinwand explained that pTOS is produced by snake gut bacteria but is not naturally found in mice; it does appear at low levels in human urine after meals but has been overlooked because most research uses rodents as models. "We've basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have," said Leinwand.
She noted previous drugs like Ozempic were inspired by reptile hormones as well. Leinwand, Long, and colleagues have formed Arkana Therapeutics to explore commercial applications based on these findings.
Looking ahead, the researchers plan further studies on how pTOS functions in humans and will investigate other metabolites found in python blood after feeding. "We're not stopping with just this one metabolite," said Leinwand. "There's a lot more to be learned."
