While we understand that exercise is good for our well-being, there is still much to learn about the complex and diverse ways physical activity promotes positive health outcomes in humans. Scientists studying the molecular details of this relationship have made a major discovery by identifying a modified amino acid that spikes in the blood after intense exercise and travels to the brain to suppress hunger and, in turn, weight loss to advance
“We’re all generally aware that physical activity is beneficial,” said Jonathan Long, an assistant professor of pathology at Stanford University who led the research. “It’s good for body weight and glucose control. But we wanted to take a closer look at this concept — we wanted to see if we could decompose exercises in terms of molecules and pathways.”
To that end, Long and other study authors from the University of California, Davis and Baylor College of Medicine turned to a technique called metabolomics. This meant using mass spectrometry to track the concentration of different molecules in tissue and blood samples and how exercise caused certain molecules to rise and fall.
First, this was applied to mice that had to complete a short session on a treadmill, after which the scientists were able to locate a large spike in a specific molecule. Next came the analysis of blood from racehorses, where the team again saw a spike in the same mysterious molecule after training.
“I remember seeing that and thinking, ‘OK, here’s something,'” Long said.
The team then relied on a separate study conducted at Stanford University in which genetic researchers measured increases in various molecules in humans during and after exercise sessions. Not only had these results revealed spikes in the same molecule, but this team had also broken down its chemical formula, showing it was a mixture of two naturally occurring chemical compounds: lactate and phenylalanine.
Lactate creates that burning sensation when we train our muscles to the point of exhaustion, while phenylalanine is an amino acid that acts as the building block for proteins. Together they form a molecule the scientists call Lac-Phe, and further research showed that it’s catalyzed by a protein called CNDP2, which is highly active in immune cells. Mice lacking this protein were unable to produce Lac-Phe, causing them to eat more and gain more weight than a control group with normal CNDP2 activity.
In another round of experiments, the scientists administered the Lac-Phe molecule to a group of obese mice. This suppressed their food intake by about 30 percent, which in turn reduced their body weight, reduced fat, and improved glucose tolerance, which Long says “suggests a reversal of diabetes.”
“We were like, ‘Wow, all this evidence really suggests that Lac-Phe goes to the brain to suppress food intake,'” he said.
While the findings are important for our understanding of how exercise mediates hunger levels and may have subtle and indirect weight loss benefits that go beyond simply burning calories, the scientists emphasize that the research is still in its infancy. Translating this discovery into a kind of “diet pill” that suppresses appetite will go a long way, beginning with a better understanding of how Lac-Phe suppresses hunger signals and identifying the receptors in the brain that enable this effect.
“Regular exercise has been shown to help with weight loss, regulate appetite and improve metabolic profile, particularly in overweight and obese people,” said co-author Dr. Yong Xu of Baylor College of Medicine. “If we can understand the mechanism by which exercise triggers these benefits, then we can bring many people closer to improving their health.”
The research was published in the journal Nature, and you can hear some of the researchers in the video below.
Exercise Induces Appetite Suppressing Molecules | 90 seconds with Lisa Kim
Sources: Stanford University, Baylor College of Medicine