Scientists previously identified GLP-1 analogs through the Gila monster, and now a metabolite present in python blood is also showing exciting prospects for future obesity treatments—potentially avoiding some troubling side effects associated with GLP-1 inhibiting medications. The findings of this study were detailed in the journal Nature Metabolism.
Pythons possess a truly extreme metabolic profile. They can go for months without a meal, only to subsequently consume an entire antelope whole.
While such dramatic fluctuations in body weight would cause irreparable health damage to other creatures, snakes have evolved unique adaptations that enable them to survive such an erratic lifestyle.
Following a meal, their metabolism ramps up by a factor of 40; the heart size of certain species can expand by up to 24.5 percent; and their gut microbiome is primed to feast on the rare bounty that is a python’s meal.
It is these bacterial byproducts that scientists might one day harness for human benefit.
Biologists Leslie Leinwand from the University of Colorado Boulder and Jonathan Long from Stanford University joined forces to investigate precisely what circulates in the bloodstream of ball pythons (Python regius) and Burmese pythons (Python bivittatus) following feeding.
Two hundred and eight distinct metabolites were found to have significantly elevated concentrations after the pythons’ monthly feedings, yet one compound stood out especially.
The levels of para-tyramine-O-sulfate, or pTOS, in the python blood surged a thousandfold after ingesting food.
This metabolite is generated by the snake’s gut bacteria during the breakdown of the common amino acid tyrosine, resulting in the release of carbon dioxide and the attachment of a sulfate group to the original molecule.
However, very little is known about pTOS. The researchers located a handful of studies suggesting pTOS circulates in humans, and a few more indicating its concentration might rise post-meal.
This information is insufficient to definitively state what impact pTOS has on people, but it was enough to motivate the researchers to delve deeper.
“If we really want to grasp metabolism, we need to look beyond just mice and humans and study the most extreme metabolic events nature has to offer,” Long states.
They discovered that while pTOS doesn’t appear naturally in mice or rats (the animals predominantly used for studying and testing potential human therapies), it does influence their appetite.
Both obese and lean male mice ate considerably less food after receiving high doses of pTOS, whether administered via injection into the abdomen or orally. This weight reduction occurred without the typical associated gastrointestinal distress, loss of muscle mass, or drop in energy levels.
In both mice and pythons, the pTOS dose activated neurons within the ventromedial hypothalamus—the brain’s control center responsible for satiety, hunger, and energy balance—which could explain how this molecule signals to the python that it doesn’t need to consume that antelope.
Leinwand and her team are hopeful that this metabolite could be utilized to achieve a similar effect in humans.
“We have essentially found an appetite suppressant that works on mice without some of the side effects common to GLP-1 drugs,” Leinwand notes.
It remains a significant distance before this substance could be deemed viable for medical applications, and many other metabolites still require investigation.
About the Author
