The origin of the appetite suppressant effect of intense exercise

The origin of the appetite suppressant effect of intense exercise< /p> UPDATE DAY

Exciting new results show that vigorous exercise causes the muscles to release a new metabolite, lactoyl-phenylalanine, which causes a decrease in appetite.

The health benefits of regular exercise are well established, with no less than 35 distinct diseases whose development is influenced, to varying degrees, by physical activity1. However, for many people who join an exercise program, it is not these benefits that represent the main source of motivation, but above all the prospect of losing weight. This goal can be frustrating, as it is generally accepted that exercise generally has a rather mixed impact on body weight, for two main reasons:

  1. amounts of exercise required to burn the calories in certain foods can be astronomical and nearly impossible to achieve on a daily basis (the 1000 calories in a simple trio of fast food requires a good hour of jogging);
  2. the increased energy expenditure caused by exercise often exerts an increase in appetite to compensate for the calories lost. 

A new metabolite

This link between appetite and exercise is very mysterious, however: some people feel terribly hungry in the hours following a workout, while others have a loss of appetite. Since appetite is largely controlled by substances that act in the brain (the hormones leptin and ghrelin, for example), it is therefore possible that these differences are caused by the presence (or absence) of molecules released in the circulation in response to exercise.

To test this possibility, scientists have used extremely sensitive modern biochemical approaches (called metabolomics), capable of detecting variations in the quantity of a large number of molecules caused by a given condition. In this case, the researchers placed mice on treadmills and ran them at higher and higher speeds until they were exhausted. 

By analyzing the composition of the blood before and after the exercise, they were thus able to compare the levels of thousands of molecules in the rodents' blood and identify those which showed the greatest variations. Amazing work!

Of all the molecules analyzed, a metabolite called lactoyl-phenylalanine (lac-Phe) showed the greatest increase following intense exercise2. This molecule is a derivative of the amino acid phenylalanine linked to lactate, formed by an enzyme (CNDP2) in response to the large amounts of lactate generated by muscle metabolism during exercise.  

< p>This phenomenon appears to be a widespread physiological adaptation in mammals, since significant increases in lac-Phe following exercise have also been observed in racehorses (one of the animals with the highest athletic performance) and in humans subjected to high intensity training.

Low appetite

Subsequent experiments suggest that lac-Phe may play a role in post-exercise appetite control. For example, the administration of this metabolite to obese mice, which generally eat with great appetite, caused a 30% decrease in their caloric intake in the following 12 hours. This decrease in appetite seems to be really due to lac-Phe, because genetically modified mice lacking CNDP2, and therefore unable to form lac-Phe, instead showed an increase in post-exercise appetite.

The study suggests that the intensity of exercise determines the amount of lac-Phe generated by the muscles. 

For example, when volunteers were subjected to high-intensity exercise (several 30-second bouts of stationary cycling at maximum intensity, interspersed with breaks), lac-Phe blood levels increased 10-fold compared to rest. A lower intensity increase (2.5-fold) was observed after less demanding effort (resistance exercise with weights), while milder exercise (stationary bicycle at moderate speed for 90 min) increased rates. of lac-Phe by approximately 1.5 times. 

In other words, the amounts of lac-Phe generated by the muscles are directly proportional to the intensity of the effort expended, suggesting that the more demanding the exercise, the better the post-exercise appetite reduction will be.&nbsp ;

The best way to avoid cravings after training and the absorption of excess calories therefore seems to increase the intensity of the exercise performed. This makes a lot of sense from an evolutionary perspective, because a sudden and intense expenditure of energy can be interpreted by the brain as a signal to flee from danger. In such a situation, now is not the time to think about the next meal!

♦ 1. Booth FW et al. Lack of exercise is a major cause of chronic diseases. Comp. Physiol. 2012; 2: 1143-211.

♦ 2. Li VL et al. An exercise-inducible metabolite that suppresses feeding and obesity. Nature, published June 15, 2022.