Indiana Jones’ greatest fear may be obesity’s biggest enemy.
Scientists at three universities have turned to nature to find a property that rivals the benefits of GLP-1 drugs without the laundry list of side effects.
What they’ve discovered, in the cold blood of a creature that grows up to 33 feet long, is poised to shake up the competition.
Up to now, GLP-1 medications have had a stranglehold on the pharmaceutical market, with hundreds more in the works. But despite the public relations power of GLP-1-mania, studies show a steep drop-off in use after a year — inspiring some researchers to probe for wilder alternatives.
Leslie Leinwand, a distinguished professor of Molecular, Cellular and Developmental Biology at the University of Colorado Boulder, has been studying pythons in her lab for decades, according to CU Boulder Today.
Native to tropical regions of Africa, Asia and Australia, these non-venomous reptiles swallow their prey whole — including deer that can weigh close to 80 pounds.
For this study, published in “Nature Metabolism,” senior author Leinwand paid close attention to the volume of food these snakes consume at one time. A single meal satiates them for months, without sacrificing metabolic balance or muscle mass.
Leinwand has found that the hours after they eat are a critical time: Their hearts expand by 25% “and their metabolism speeds up 4,000-fold to help them digest their meal,” according to CU Boulder.
Jonathan Long, an associate professor of pathology at Stanford School of Medicine, specializes in the study of metabolites, the substances in the blood that fuel metabolism. The two researchers partnered up to try to unlock the mysteries of the python’s biology.
Long, who typically studies mammals, told CU Boulder that “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.”
That’s where the python slithers in.
The team behind this study collected blood samples from two python species, ball and Burmese, immediately following their meals, administered every 28 days.
Of the more than 200 metabolites the researchers identified in the blood samples, one stood out for its elasticity: para-tyramine-O-sulfate (pTOS).
That isolated metabolite was sent to Baylor University, where researchers gave a set of obese and lean mice high doses of pTOS. The metabolite noticeably affected the hypothalamus — the part of the brain that controls appetite — and triggered weight loss in the mice.
The kicker? None of the rodents experienced muscle or energy loss, or gastrointestinal issues.
Pythons produce pTOS in their guts, and while low levels of the metabolite are also found in human urine, pTOS does not naturally occur in mice. This could help to explain why the compound hasn’t yet been considered for weight loss, since most research for this class of drugs is performed on mice and rats.
GLP-1 drugs as we know them were actually first inspired by the venom produced in a different reptile, the Gila monster, whose saliva has a hormone similar to the GLP-1 hormone in humans.
But the many side effects of the synthesized version found in Wegovy, Ozempic and others have deterred large portions of the drugs’ millions of users from continuing what are meant to be long-term, if not lifelong, medications.
Leinwand and Long, as well as some of Leinwand’s CU Boulder colleagues, have launched Arkana Therapeutics, a start-up that they hope will someday produce a synthetic version of python metabolites that may be able to replace standard GLP-1s for people especially sensitive to the side effects.
“This is a perfect example of nature-inspired biology,” Leinwand said of her team’s new study.
“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.”
