Python blood could hold the secret to healthy weight loss

Postdoctoral researchers Skip Maas, left, and Marta Furtado hold Maas’ pet pythons in the Leinwand Lab. Maas studies python metabolism in addition to keeping the snakes as pets.

CU Boulder researchers have discovered an appetite-suppressing compound in python blood that helps the snakes go months without eating yet remain metabolically healthy.  

The research could inform new weight loss therapies that promote satiety without the nausea, muscle wasting and other side effects that can come with existing obesity drugs.  

“This is a perfect example of nature-inspired biology,” said Leslie Leinwand, executive science officer at the BioFrontiers Institute and 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 superheroes 

Pythons can grow as big as a telephone pole, swallow an antelope whole, and fast for more than a year afterward—all while maintaining a healthy heart and plenty of muscle mass. In the hours after they gorge, their heart expands 25% and their metabolism speeds 4,000-fold to help them digest their colossal meal. 

To better understand what compounds in the body make these superpowers possible, Leinwand’s team measured blood samples from ball pythons and Burmese pythons, fed once every 28 days, immediately after they ate. They found 208 distinct metabolites (tiny molecules the body produces as it breaks down food) that increased significantly after the pythons dined. One, called para-tyramine-O-sulfate (pTOS), soared 1,000-fold.

To learn what this little-known metabolite does, the team gave high doses of pTOS to obese mice. They discovered that it acted on the hypothalamus, the appetite center of the brain, prompting weight loss without gastrointestinal problems, muscle loss or declines in energy.

PTOS is produced by the snake’s gut bacteria and is not present in mice naturally. It is present in human urine at low levels and does increase somewhat after a meal. But, to date, very few researchers have studied it.

“We’ve basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have,” Leinwand said, referring to weight loss drugs like Ozempic and Wegovy, which act on the hormone glucagon-like peptide-1 (GLP-1). 

Nature-inspired weight loss 

Leinwand noted that those blockbuster 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 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,” Leinwand said.  With support from Venture Partners at CU Boulder, the campus commercialization arm, she and her colleagues have formed a startup, Arkana Therapeutics, to work toward commercializing some of the lessons they’re 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. 

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.

“We’re not stopping with just this one metabolite,” Leinwand said. “There’s a lot more to be learned.”