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���Ҵ�ý�ƽ������ 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 Medicine and Baylor universities, could inform new weight loss therapies that promote satiety without the nausea and muscle loss that can come with existing drugs.

Professor Leslie leinwand, left, and PhD candidate Skip Maas look on at Maas's pet pythons during their visit to the lab. In addition to keeping pet pythons, Maas studies python metabolism.��

The findings were published in the journal .

“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 superheroes

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 School of Medicine 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 weight loss therapies

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 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 ���Ҵ�ý�ƽ������ 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.”