Further experiments determined that pTOS is a byproduct of the breakdown of tyrosine — an amino acid present in dietary protein — by bacteria in the gut. Treating the pythons with antibiotics prior to feeding abolished the eating-associated increase in pTOS levels.

“We were able to work out a pathway in which pTOS is produced after a meal through the metabolism of tyrosine in the gut and the liver,” Long said. “We also found that it then goes to a region of the brain called the hypothalamus, which is a well-known regulator of energy homeostasis. There it activates neurons involved in regulating feeding behaviors.”

The metabolite in humans

The researchers then studied six publicly available datasets of blood from healthy volunteers before and after a meal. In five of the six, pTOS levels were elevated after eating, but only by about two- to fivefold. Such a small increase in humans would be extremely difficult to pick out among many other feeding-associated metabolic changes — illustrating the value of using pythons as a model animal.

But a few people were more snakelike than others. One individual in the databases experienced a more than 25-fold increase in pTOS after a meal, reaching python-level concentrations in their blood. (Because these datasets were from previously conducted studies, it is not possible to know whether this person felt more full or ate less than other study participants.)

Although more research needs to be conducted into the possible use of pTOS in humans to curb appetite, the pythons gave the researchers a plethora of additional molecules to study.

“We’re generating a landscape of molecules that vary in prevalence after eating in all organs of these snakes,” Long said. “We already found many that look like hormones but that have no similarity with any known hormones in mice or humans. This is a form of natural product discovery.”

Long and his colleagues speculate that, like blood pressure medications and anticoagulants, some of these molecules could be clinically useful. “Maybe a patient with Type 1 diabetes due to defective beta cell function could benefit from a snake molecule that stimulates cell division, or a person with liver disease could take a snake-derived drug that facilitates organ remodeling,” Long said.

He noted that there’s an interest among scientists in augmenting human capabilities, such as creating vaccines that enhance the immune response. “Maybe this concept of using molecules first identified in snakes or other animals can extend to many other aspects of human health,” he said.

“We’re excited to learn from these snakes and other ‘extreme’ animals to inspire future discoveries,” he added.

The study was funded by the National Institutes of Health (grants R01GM029090, R01DK138518, R01DK105203, R01DK124265, K99DK141966, K99AR081618, F32HD112123, F32HL170637, F32DK138685 and T32GM142607), the Wu Tsai Human Performance Alliance, the Stanford Diabetes Research Center, the Phil and Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, the Ono Pharma Foundation, the Leducq Foundation, the American Heart Association, and the Stanford University Medical Scientist Training Program.