University of Colorado study finds python blood could lead to weight loss drug with fewer side effects

A compound found in python blood could lead to a new kind of weight loss drug, one that suppresses appetite without some of the side effects linked to popular medications like Ozempic.

Researchers at the University of Colorado Boulder, working with scientists at Stanford University and Baylor University, are studying how Burmese pythons regulate appetite after eating massive meals.

Skip Maas, a molecular biologist who recently completed his Ph.D. at CU Boulder, has spent years studying snake biology and how it might translate to human health.

"They are such extreme feeders," Maas said. "They'll go for multiple months at a time without eating, and then when they do eat, they can eat up to their body weight in one meal."

After analyzing blood samples from pythons following a meal, researchers identified hundreds of metabolites, or chemicals the body produces as it breaks down food. One stood out. A compound called para-tyramine-O-sulfate, or pTOS, which increased more than 1,000-fold after feeding, even as the snake's overall metabolism surged.

"Their metabolism increases by about 40-fold after eating, which is the equivalent of a Kentucky Derby racehorse going from standing to sprinting at the Derby, which is massive," Maas said. "But pythons are doing this not just for a lap around the track, but for about six days straight."

The goal isn't to turn people into pythons, it's much more practical: help them eat less without the side effects seen in current drugs.

When they gave pTOS to mice, the animals ate less and lost weight over the course of about a month. They did not stop eating entirely but showed a consistent reduction in how much they consumed.

"They didn't go all day without eating like pythons, but they still ate less food and lost weight," Maas said.

The findings suggest the compound works differently from widely used GLP-1 drugs such as Ozempic and Wegovy, which affect the brain, gut, and pancreas. While effective, those medications can slow digestion and cause side effects such as nausea.

"It's (GLP-1s) also releasing insulin in your pancreas. And so that's what makes it a really good diabetes drug, but if you're taking it for weight loss, then that's something you don't normally want, extra insulin when you don't need it," Maas said.

The python-derived compound appears to act only in the brain, targeting the hypothalamus, the region that regulates hunger, without affecting digestion or insulin levels.

"It only affects that mental feeling of satiety, that desire not to eat, and so ideally, this could be a weight loss drug that doesn't have those side effects," Maas said.

Maas said the appetite findings are just one piece of a much larger picture. His primary research focuses on how snakes can go months without eating while preserving muscle, something that could have implications for aging, injury recovery, and disease.

"Snakes are incredibly resistant. So, what really excites me is trying to figure out how that works, how they can go so long without eating but not really suffer any ill effects from that. And so, I have found a few things out. There's still more work I want to do with it, but in ways that they tune and regulate their overall muscle protein and muscle energy consumption is really, really nifty, and I've now also translated that to mice as well," Maas said.

The research is still in early stages, and human trials are not currently underway at CU Boulder, but Maas said he is hopeful the weight loss application will eventually move in that direction.

"If we can find the funding to look at this drug in a human context, that'd be ideal," he said.