You might think that human eating patterns have little in common with giant snakes that kill their prey by slowly suffocating it, swallowing it whole and then not eating again for another three weeks or so.
You would be wrong.
A multi-site team of researchers, co-led by Yong Xu, MD, PhD, of the USF Health Morsani College of Medicine, has shown that a newly discovered metabolite, or tiny molecule produced as the body breaks down food, functions the same way in people and in pythons. Other research leaders on the team include scientists from Stanford University, the University of Colorado and Baylor College of Medicine,
Ultimately, the metabolite, called pTOS, works to inhibit feeding, says their new study, “Python metabolomics uncovers a conserved postprandial metabolite and gut–brain feeding pathway,” published this month in Nature Metabolism, providing potential new insight into how obesity in humans could be managed.
The research team’s findings suggest that the novel metabolite dramatically increases after a python eats a big meal — and that the same phenomenon occurs in people.
“We discovered, using our lab model system, that pTOS functions as a postprandial signal to regulate brain hypothalamic neurons and inhibit feeding,” said Dr. Xu, a co-corresponding author of the study.
The team reached their conclusion after studying the metabolites blood from pythons that either had fasted or had just eaten a large meal. They found that the pTOS metabolite increased by more than 1,000-fold in python blood after eating. In the process, they discovered that humans also have pTOS in their blood after a meal. In lab experiments, they learned that synthetic pTOS activates neurons in the hypothalamus, a well-established feeding center of the brain and this, in turn, reduces food intake and potentially body weight.
The acronym pTOS stands for para-tyramine-O-sulphate.
Dr. Xu, who joined USF Health last year as director of the Center for Molecular Psychiatry in the Department of Psychiatry and Behavioral Neurosciences, has spent the past decade immersed in research to identify novel neural circuits, neurotransmitters and signals that are crucial for coordinated control of body weight, glucose balance and the web of cues, needs and rewards known as “feeding behavior:” the why, when and what we eat.
In this study, Dr. Xu and the research team identified a diet-derived metabolite that functions as a systemic signal that can suppress feeding.
“Importantly, these findings expand the classical peptide-centric view of gut-brain communication to also include small molecule metabolites,” Dr. Xu said. “We now know that pTOS clearly suppresses feeding, although it does not alter energy expenditure. Our next step is to define the molecular targets of pTOS in the brain, including the identity of pTOS receptors, and to determine whether this pathway can be engaged in humans.”
Ultimately, further research about how pTOS makes eating less appealing could provide possible avenues to develop new classes of weight-loss medications, although Dr. Xu cautioned that gaining this knowledge will take several more studies.