Major scientific breakthrough towards the benefits of exercise in a pill


Exercise Pill Fitness Supplements

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

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

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

“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, 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 can bring many people closer to improving their health.”

“We wanted to understand how movement works at the molecular level in order to capture some of its benefits,” said co-corresponding author Jonathan Long, MD, an assistant professor of pathology at Stanford Medicine and Institute Scholar of Stanford ChEM-H (Chemistry, Engineering, and medicine for human health). “For example, elderly or frail people who can’t get enough exercise could one day benefit from taking a drug that can slow down osteoporosis, heart disease or other conditions.”

Xu, Long and their colleagues conducted extensive blood analysis[{” attribute=””>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

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