The media is rife with anecdotal accounts of patients hiding their use of GLP-1 weight-loss drugs, passing off their success on mysterious newfound reserves of self-discipline. The simple reason, I believe, is that these medical interventions are not sick, twisted, based, or metal.
But researchers have found what they’re calling a “perfect example of nature-inspired biology,” with potential as an arguably much cooler weight-loss medication: metabolites from the blood of Burmese pythons.
Scientists at Stanford University, Baylor, and the University of Colorado Boulder collaborated on the effort, which started with a hunt for the unique chemical signals that allow pythons to go months—even a year or more—between their giant, jaw-unhinging meals. What makes the discovery so promising, however, is that the researchers also found that this metabolite, para-tyramine-O-sulfate (pTOS), is also produced naturally (albeit in more minute quantities) in humans after they’ve had a large meal themselves.
Study coauthor Jonathan Long, a member of Stanford’s Wu Tsai Neurosciences Institute, credited the discovery to the team’s willingness to go extreme.
“If we truly want to understand metabolism,” Long said in a statement, “we need to go beyond looking at mice and people and look at the greatest metabolic extremes nature has to offer.”
Made by both human and python gut bacteria
Metabolites are a broad category of small molecules. Any intermediate or final product a living thing makes while breaking something down into energy and/or the raw materials it needs to grow qualifies. And in the case of the Burmese python, the researchers had a lot of them to comb through.
The team fed meals consisting of about 25% of their snake’s body weight to test groups of younger, smaller (more manageable) Burmese pythons, each weighing about 3.3 to 5.5 pounds (1.5 to 2.5 kilograms). The snakes produced at least 208 unique metabolites as a result of their big overdue meals, researchers said.
All of these compounds spiked to over 32 times their normal concentration in the pythons’ blood in the hours after eating—but pTOS concentrations leapt up to over a thousand times their normal levels.
“[W]hen we administered pTOS to laboratory mice at levels similar to what we saw in the pythons after eating, we didn’t see any effect on energy expenditure, beta cell proliferation or organ size,” Long explained in a statement. “What it did regulate was the appetite and feeding behaviors of the mice.”
In other words, pTOS provided appetite-suppressant signals without causing any loss of energy, gastrointestinal problems, or muscle loss.
“We’ve basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have,” said the study’s senior author, Leslie Leinwand, a distinguished professor of molecular, cellular, and developmental biology at CU Boulder.
Further study explained why: the high doses of pTOS acted on the hypothalamus, a region of the brain known to manage hunger, thirst, and other physiological moods, like sex drive and sleepiness. (GLP-1s, by contrast, act on a host of organs in the body, including the pancreas and the stomach.)
In follow-up research, the team found that pTOS was produced by the breakdown of tyrosine, a common amino acid in protein, by bacteria in the gut and liver. While mice do not produce pTOS, tests of human urine showed that we do in small amounts, particularly after eating.
A bright future for snake-based medicine
The researchers hope to continue studying the other metabolites that spiked in their lab pythons. Some appeared at as high as 500% to 800% above their baseline levels after the snakes’ large meals.
Perhaps counterintuitively, this practice has a long history. Compounds derived from snake venom, for example, have led to the development of new blood pressure medications and anticoagulants, medications capable of treating deadly blood clots. Even GLP-1s have something of a cool backstory: the popular peptide-based medication reportedly was inspired by a hormone in the venomous Gila monster. (Advertisers should lean on that more.)
“We’re excited to learn from these snakes and other ‘extreme’ animals to inspire future discoveries,” Long said. “Obviously, we are not snakes. But maybe by studying these animals we can identify molecules or metabolic pathways that also affect human metabolism.”
Source: gizmodo.com
