Python blood compound could lead to new weight loss treatment

Researchers at the University of Colorado Boulder have found an appetite-suppressing compound in python blood that helps snakes eat more food and go months without eating but remain metabolically healthy.

The research, in collaboration with scientists at Stanford and Baylor universities, could inform new weight-loss treatments that promote satiety without the brain and muscle loss that comes with existing drugs.

The findings appear March 19 in the journal Nature Metabolism.

“This is a great example of biology inspired by nature,” said Leslie Leinwand, Distinguished Professor of Molecular, Cellular and Developmental Biology, who has been studying pythons in her lab for two decades. “You look at unusual animals that can do things that you and I and other mammals can’t, and you try to use that for therapeutic interventions.”

Metabolic superpowers

A python can grow as large 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. During the hours they eat, Linwand’s research showed, their heart expands by 25% and their metabolism speeds up 4,000 times to digest their food.

To better understand what makes these superpowers possible, Linwand teamed up with Stanford University pathology professor Jonathan Long, who studies metabolic byproducts, or metabolites, in the blood to understand how mammals take in and use energy.

Long’s lab recently examined the blood of another fascinating creature—the racehorse—for insight into how animals can endure all those sprints.

“If we’re really going to understand metabolism, we have to go beyond looking at mice and people and look at the greatest range of metabolism that nature has to offer,” Long said. Long said.

For the new study, the team measured blood samples from ball pythons and Burmese pythons, which were fed once every 28 days, immediately after they ate.

In all, they found 208 metabolites that increased significantly after the pythons ate them. A molecule called mercury tyramine sulfate (pTOS) increased 1,000-fold.

Other studies, conducted with Baylor University researchers, showed that when they gave high doses of pTOS to obese or lean mice, it acted on the hypothalamus, the brain’s appetite center, to lose weight without causing stomach problems, muscle loss or energy loss.

The study found that pTOS, which is produced by snake gut bacteria, does not exist naturally in mice. It is present in low levels in human urine and increases slightly after meals.

But because most research is done in rats or mice, 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,” Linwand said, referring to drugs like Ozempic and Vigovi that act on glucagon-like peptide-1 (GLP-1).

Nature inspired biology

Linwand noted that this new drug was inspired by another real one, the Gila Monster. Gila monster venom contains a hormone similar to human GLP-1.

These drugs are now used by millions, but research shows that half of the people who use them stop taking them within a year.

We believe there is still room for therapeutic growth in this market.”

Leslie Canvas, Senior Writer

She, Long and her CU Boulder colleagues have formed a startup called Arcana Therapy to work toward commercializing some of the lessons they’re learning from pythons.

They envision a day when chemically synthesized analogs of rare metabolites found in pythons can be turned into treatments to help people.

Weight loss isn’t the only treatment goal they’re looking at.

Age-related muscle loss, or sarcopenia, affects almost everyone as they age, and people who have health problems that make it difficult for them to exercise are particularly hard hit. To date, there is no medication to prevent or reverse sarcopenia.

Linwand said snakes may offer insight into how to do this.

In future research, the team hopes to find out how pTOS works in humans and to list the activity of other metabolites that increase after eating pythons. Some of the metabolites that the researchers identified in their research increased by 500 to 800%.

“We didn’t just stop with this one metabolite,” Linwand said. “There’s a lot to learn.”