Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear.
Researchers from Baylor College of Medicine, Stanford School of Medicine and collaborating institutions have found a molecule in the blood that is produced during exercise that can effectively reduce food intake and obesity in mice. Their findings appear in the journal Nature.
The researchers wanted to understand how exercise works at the molecular level to be able to understand the benefits that it has.
Lac-Phe a Molecule Produced During Physical Activity Can Suppress Food Intake
For the study, the team performed comprehensive analyses of blood plasma compounds from mice following intense treadmill running, and the most significantly induced molecule was a modified amino acid called Lac-Phe that is synthesized from lactate and phenylalanine.
They found that 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.
The team then administered Lac-Phe to mice for 10 days and found a reduced cumulative food intake and body weight, and improved glucose tolerance.
The enzyme identified involved in the production of Lac-Phe is called CNDP2. The team also encountered robust elevations in plasma Lac-Phe levels following physical activity in racehorses and humans. One exercise cohort showed that sprint exercise-induced the most dramatic increase of Lac-Phe, followed by resistance training and then endurance training.
The team is set to investigate how the molecule mediates its effects on the body. They want to learn to modulate this pathway to use it for therapeutic interventions.
Baylor College of Medicine. “The benefits of exercise in a pill? Science is closer to that goal.” ScienceDaily. ScienceDaily, 15 June 2022.
Li, V.L., He, Y., Contrepois, K. et al. An exercise-inducible metabolite that suppresses feeding and obesity. Nature 606, 785–790 (2022). https://doi.org/10.1038/s41586-022-04828-5