Research highlight

An exercise-inducible molecule that suppresses appetite

Nature

June 16, 2022

A metabolite produced during exercise that can effectively reduce food intake and obesity in mice is identified in a study published in Nature. The findings improve our understanding of the physiological processes that underlie the interplay between exercise and hunger.

Physical activity has been proven to protect against obesity and obesity-associated diseases, as the increased energy demand requires our bodies to burn more calories. However, the longer-term benefits of exercise for physiology and metabolic health are still poorly understood. Jonathan Long and colleagues conducted comprehensive analyses of blood plasma metabolites from mice following intense treadmill running. The most significantly induced metabolite was a modified amino acid called Lac-Phe that 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).

A high dose of Lac-Phe suppressed food intake in mice with diet-induced obesity (fed a high-fat diet) by about 50% compared to control mice over a period of 12 hours without affecting their movement or energy expenditure. Administration of Lac-Phe to the mice for 10 days reduced cumulative food intake, reduced body weight (owing to loss of body fat) and improved glucose tolerance. The authors also identified an enzyme 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. However, the appetite-suppressing effect of Lac-Phe existed only after exercise, not in the sedentary state, and was observed only in mice made obese by a high-fat diet.

Robust elevations in plasma Lac-Phe level following physical activity were also observed 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. The metabolic effects of Lac-Phe were not investigated in the human cohorts. Further studies are needed to uncover the downstream pathways of Lac-Phe action and to provide more insights into new therapeutic opportunities and the benefits of physical activity for human health, the authors conclude.

doi: 10.1038/s41586-022-04828-5

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