The groundbreaking discovery of GLP-1 receptor agonists, exemplified by medications like Ozempic, originated from insights gleaned from the Gila monster. Now, emerging research suggests that a specific compound found in python blood holds considerable potential for future weight management therapies, possibly offering an alternative with fewer adverse effects than current GLP-1 treatments.
Pythons are characterized by exceptionally robust metabolic systems. These reptiles can endure prolonged periods without sustenance for months, only to consume entire prey animals afterward.
While such extreme fluctuations in caloric intake would prove detrimental to the physiological integrity of most creatures, snakes have evolved specialized adaptations enabling them to flourish amidst this unpredictable feast-or-famine existence.
Post-ingestion, their metabolic rate escalates by a factor of forty times; for certain species, their cardiac output can increase by as much as 24.5 percent; and their gut microbiome is meticulously prepared to capitalize on infrequent feeding opportunities.
It is plausible that the metabolic byproducts generated by these symbiotic microorganisms could, in the future, be leveraged for human therapeutic applications.
Biologists Leslie Leinwand from the University of Colorado Boulder and Jonathon Long of Stanford University collaborated to investigate the substances present in the blood of ball pythons (Python regius) and Burmese pythons (Python bivittatus) subsequent to their feeding episodes.
A total of 208 distinct metabolites showed a marked increase following the pythons’ infrequent, monthly meals, yet one particular compound garnered significant attention.
Concentrations of para-tyramine-O-sulfate, identified as pTOS, surged by a remarkable 1,000-fold in the circulation of pythons in the postprandial state.
This metabolite is synthesized by the snake’s intestinal flora during their enzymatic breakdown of the common amino acid tyrosine, a process that results in the liberation of carbon dioxide and the addition of a sulfate group to the molecule.
However, our understanding of pTOS remains limited. The research team identified a small number of studies indicating that pTOS is indeed present in the human circulatory system, with some suggesting it may elevate following nutrient intake.
While these findings are insufficient to definitively ascertain the physiological impact of pTOS on humans, they provided sufficient impetus for the investigators to conduct more in-depth examinations.
“To genuinely comprehend metabolic processes, it is imperative to broaden our scope beyond conventional model organisms like mice and humans, and instead, explore the most profound metabolic extremes that nature presents,” stated Long.
Their investigations revealed that while pTOS does not appear to occur naturally in murine models or rats—organisms frequently employed for the study and evaluation of potential human therapies—it does exert an influence on their appetite.
Both overweight and lean male mice exhibited a significant reduction in food consumption subsequent to receiving substantial doses of pTOS, administered either via intraperitoneal injection or oral gavage. This resulted in weight reduction without the accompanying gastrointestinal disturbances, loss of lean muscle mass, or diminished energy levels commonly associated with such interventions.
In both pythons and mice, the administration of pTOS stimulated neuronal activity within the ventromedial hypothalamus, the brain region responsible for regulating satiety, hunger, and energy homeostasis. This mechanism likely accounts for how the molecule signals to the python that further ingestion, such as consuming an antelope, is unnecessary.
Leinwand and her colleagues aspire to explore the potential repurposing of this metabolite to achieve comparable outcomes in humans.
“We have effectively identified an appetite suppressant that demonstrates efficacy in mice, devoid of some of the adverse effects characteristic of GLP-1 medications,” commented Leinwand.
Considerable research and development are still required before this discovery can be translated into a clinically viable human therapeutic. Furthermore, numerous other metabolites warrant exploration to fully understand their potential applications.
