Could the “exercise molecule” become an “exercise pill”?

Exercise alters more than 9,800 molecules in the blood, a process scientists have called a cellular “symphony.”

“You get such a dramatic change when you exercise and it’s something that permeates your entire system,” said Michael Snyder, chairman of the department of genetics at Stanford University. THIS DAY. We think it’s a global regenerator, so to speak… there’s not a lot of things that can give you that.”

But not all of these molecules provide the same benefits of physical activity. Last week, researchers based primarily at Baylor School of Medicine and Stanford School of Medicine reported that one in particular appears to play an outsized role. They detailed finding him in the diary. Nature.

Lac-Phe

The large team of more than two dozen scientists used a strategy called untargeted metabolomics to see what happens to molecules in the blood plasma of mice after the creatures ran on a treadmill to exhaustion. The noticeable increase was a compound with the chemical formula C12H14NO4, which researchers later discovered was N-lactoyl-phenylalanine, or “Lac-Phe” for short. The modified amino acid is synthesized from lactate (which is produced in abundance during intense exercise) and phenylalanine, one of the building blocks of protein.

They also replicated the mouse experiment in racehorses and found that Lac-Phe is the “most significantly induced circulating metabolite.” Later, they observed how Lac-Phe levels rose sharply in 36 human volunteers while they were cycling, lifting weights, or cycling to increase endurance. The researchers noted that the data “establishes Lac-Phe as one of the major exercise-regulated metabolites in humans.”

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So it seems that the blood is flooded with Lac-Phe during and after exercise, particularly when it is intense. Could it perhaps be responsible for imparting some of exercise’s miraculous health effects?

Sorry, no “exercise pill”

To find out, the researchers injected Lac-Phe into obese mice and found that it significantly reduced their appetite, reduced body fat, and improved glucose tolerance over the ten-day study period. Interestingly, Lac-Phe did not confer these benefits on healthy, lean mice, even when given at higher doses. It also didn’t work when given orally, indicating that Lac-Phe may not work as a long-sought “exercise pill.”

The researchers found further empirical support that Lac-Phe regulates the healthful effects of exercise in a trial in which they genetically engineered mice without a key enzyme for producing Lac-Phe. Compared to control mice, these mice lacking Lac-Phe lost much less weight when participating in an identical exercise program.

Mice given Lac-Phe did not experience any apparent ill effects, nor did the molecule interfere with other metabolic functions, an auspicious sign that human trials with the compound could begin relatively soon. Long-term studies may reveal that Lac-Phe may reduce the severity of osteoporosis, heart disease, diabetes, cognitive decline, and other health problems that exercise is known to treat. Although a Lac-Phe drug could never capture the full benefits of exercise, even bottling it would be a fantastic drug.

Next, the researchers intend to focus on the effects of Lac-Phe on the brain. As they wrote:

“Future work uncovering the downstream molecular and cellular mediators of Lac-Phe action in the brain may provide new therapeutic opportunities to capture the cardiometabolic benefits of physical activity for human health.”

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