Major Scientific Breakthrough Toward the Benefits of Exercise in a Pill

Scientists have identified a molecule in the blood, created during exercise, that can effectively reduce food intake and obesity in mice.

The benefits of exercise in a pill? Science is now closer to that goal.

Researchers have identified a molecule in the blood that is produced during exercise and can effectively reduce food intake and obesity in mice. The discovery improves our understanding of the physiological processes that underlie the interplay between exercise and hunger. Scientists from Baylor College of Medicine, Stanford School of Medicine, and collaborating institutions reported the findings on June 15, 2022, in the journal Nature.

“Regular exercise has been proven to help weight loss, regulate appetite, and improve the metabolic profile, especially for people who are overweight and obese,” said co-corresponding author Dr. Yong Xu, professor of pediatrics – nutrition and molecular and cellular biology at Baylor. “If we can understand the mechanism by which exercise triggers these benefits, then we are closer to helping many people improve their health.”

“We wanted to understand how exercise works at the molecular level to be able to capture some of its benefits,” said co-corresponding author Jonathan Long, MD, assistant professor of pathology at Stanford Medicine and an Institute Scholar of Stanford ChEM-H (Chemistry, Engineering & Medicine for Human Health). “For example, older or frail people who cannot exercise enough, may one day benefit from taking a medication that can help slow down osteoporosis, heart disease or other conditions.”

Xu, Long, and their colleagues conducted comprehensive analyses of blood plasma compounds from mice following intense treadmill running. The most significantly induced molecule was a modified amino acid called Lac-Phe. It is synthesized from lactate (a byproduct of strenuous exercise that is responsible for the burning sensation in muscles) and phenylalanine (an amino acid that is one of the building blocks of proteins).

In mice with diet-induced obesity (fed a high-fat diet), a high dose of Lac-Phe suppressed food intake by about 50% compared to control mice over a period of 12 hours without affecting their movement or energy expenditure. When administered to the mice for 10 days, Lac-Phe reduced cumulative food intake and body weight (owing to loss of body fat) and improved glucose tolerance.

The researchers also identified an enzyme called CNDP2 that is involved in the production of Lac-Phe and showed that mice lacking this enzyme did not lose as much weight on an exercise regime as a control group on the same exercise plan.

Interestingly, the team also found robust elevations in plasma Lac-Phe levels following physical activity in racehorses and humans. Data from a human exercise cohort showed that sprint exercise induced the most dramatic increase in plasma Lac-Phe, followed by resistance training and then endurance training. “This suggests that Lac-Phe is an ancient and conserved system that regulates feeding and is associated with physical activity in many animal species,” Long said.

“Our next steps include finding more details about how Lac-Phe mediates its effects in the body, including the brain,” Xu said. “Our goal is to learn to modulate this exercise pathway for therapeutic interventions.”

Reference: “An exercise-inducible metabolite that suppresses feeding and obesity” by Veronica L. Li, Yang He, Kévin Contrepois, Hailan Liu, Joon T. Kim, Amanda L. Wiggenhorn, Julia T. Tanzo, Alan Sheng-Hwa Tung, Xuchao Lyu, Peter-James H. Zushin, Robert S. Jansen, Basil Michael, Kang Yong Loh, Andrew C. Yang, Christian S. Carl, Christian T. Voldstedlund, Wei Wei, Stephanie M. Terrell, Benjamin C. Moeller, Rick M. Arthur, Gareth A. Wallis, Koen van de Wetering, Andreas Stahl, Bente Kiens, Erik A. Richter, Steven M. Banik, Michael P. Snyder, Yong Xu and Jonathan Z. Long, 15 June 2022, Nature.
DOI: 10.1038/s41586-022-04828-5

Baylor UniversityExerciseFitnessObesityPopular
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  • Martard

    Interesting, I wonder why phenylalanine is in there, lactate makes sense. Now to find the receptors for it, and then big pharma can ad some weird stuff on the phenylalanine like fluorine or chlorine to increase blood serum half life etc. Zombie pills

  • Earlier the Better

    ‘Lac-Phe’ is a modified amino acid; Hopefully, Everyone can take it? Why not say, Which Proteins use it to build themselves? Later on, Which Enzymes break them !

  • tom

    Sprinting/racing involves a large muscle group that is well known to burn high amounts of energy. A compound that can simulate this muscle burn might be painful. I know I have no appetite when in pain.

  • zack

    Homo sapien’s brain has evolved to be sufficiently useful to fool itself: laughable mentality:D

  • Bergþór

    Could this perhaps be modified to only allow the body to burn fat in which everyone can just take a pill then run on a treadmill for a half hour and burn 1kg of fat. (Not a doctor but have read a lot of articles of science articles) I hope this happens then everyone can be skinny and have a less likely chance of getting depression (think that’s right not sure)

  • Athokpam Bike Singh

    Exercise in a pill. Like GW501516? Anything that works is banned. They always have many side effects. Don’t be lazy, get moving.

  • Alexander Breeding

    Some of us aren’t lazy, and can’t move. I have both a spine injury and a TBI that causes severe balance issues. Since I can’t walk or run, indeed some days can’t even be upright at all, it’s extremely difficult for me to do much exercise at all. I intake very few calories to try to keep my weight stable. Something like this would be a huge benefit for those of us who lost our ability to move to war, or other circumstances.

  • Michael Scott

    Big Pharma ad:
    “This breakthrough will make it possible to eat a bowl of potato chips for breakfast, lunch and dinner everyday without exercising. Amazing!”