A surprising source – the blood of pythons – may hold the key to new weight loss therapies, according to research published today in the journal Nature Metabolism. Scientists at the University of Colorado Boulder, in collaboration with Stanford and Baylor universities, have identified an appetite-suppressing compound in python blood that could offer a novel approach to managing weight, potentially without the side effects associated with current medications.
The discovery centers around how pythons are able to consume massive meals – sometimes exceeding their own weight – and then go months without eating, all while maintaining a healthy metabolism. This remarkable ability sparked the investigation into the unique biochemical processes at play within these snakes. Understanding these mechanisms could have significant implications for addressing the global obesity epidemic and related health concerns. The research team believes this is a prime example of “nature-inspired biology,” leveraging the extraordinary adaptations of animals to develop therapeutic interventions for humans.
Unlocking the Secrets of Python Metabolism
Pythons’ metabolic feats are truly exceptional. Following a large meal, a python’s heart can expand by 25% and its metabolism speeds up an astonishing 4,000-fold to efficiently digest the food. This process doesn’t lead to the typical metabolic disruptions seen in other animals, including humans. To unravel the secrets behind this resilience, researchers teamed up with experts in metabolic byproducts. Jonathan Long, an associate professor of pathology at Stanford University, brought his expertise in studying how mammals process energy to the collaboration.
Long’s lab had previously examined the blood of racehorses, seeking insights into their endurance capabilities. As he explained, “If we truly aim for to understand metabolism, we need to go beyond looking at mice and people and gaze at the greatest metabolic extremes nature has to offer.” The team focused on ball pythons and Burmese pythons, analyzing blood samples collected immediately after the snakes consumed a meal, fed once every 28 days.
Para-Tyramine-O-Sulfate: A Key Appetite Suppressant
The analysis revealed 208 metabolites that significantly increased after the pythons ate. Among these, one molecule stood out: para-tyramine-O-sulfate (pTOS). This compound increased a remarkable 1,000-fold in the pythons’ blood after feeding. Further studies, conducted with researchers at Baylor University, demonstrated that administering high doses of pTOS to both obese and lean mice triggered weight loss by acting on the hypothalamus, the region of the brain that controls appetite. Importantly, this weight loss occurred without the gastrointestinal issues or muscle loss often associated with other weight loss drugs.
Interestingly, pTOS is produced by the gut bacteria of pythons and is present in human urine at low levels, increasing slightly after a meal. However, it has been largely overlooked in previous research due to the focus on traditional laboratory animals like mice and rats. “We’ve basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have,” said Leslie Leinwand, a distinguished professor of Molecular, Cellular and Developmental Biology at CU Boulder and senior author of the study.
Building on Nature’s Innovations
The development of current weight loss drugs, such as Ozempic and Wegovy, was similarly inspired by nature – specifically, the venom of the Gila monster, which contains a hormone similar to human glucagon-like peptide-1 (GLP-1). While these drugs have proven effective for many, studies suggest that as many as half of those who use them discontinue treatment within a year. Leinwand believes there’s still room for improvement in the market, stating, “We believe there is still room for therapeutic growth in this market.”
To capitalize on these findings, Leinwand, Long, and their colleagues have formed a start-up company, Arkana Therapeutics, with the goal of commercializing the lessons learned from pythons. Their vision is to develop chemically synthesized analogs of pTOS and other rare metabolites found in pythons into therapies for humans. Beyond weight loss, the researchers are also exploring the potential of these metabolites to address age-related muscle loss, or sarcopenia, a condition for which there are currently no effective treatments.
The team plans to continue investigating how pTOS functions in humans and to catalog the roles of the other metabolites that increase after pythons eat. Some of these metabolites showed increases of 500 to 800% in the study. “We’re not stopping with just this one metabolite,” Leinwand emphasized. “There’s a lot more to be learned.”
This research offers a promising new avenue for developing more effective and tolerable weight loss therapies, highlighting the potential of studying extreme adaptations in the natural world to address human health challenges. The next step for the team involves further research to understand the precise mechanisms of pTOS and its potential for clinical application.
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