Scientists have found a molecule produced from exercise that suppresses appetite

(ORDO NEWS) — The team of scientists conducted a comprehensive analysis of the blood metabolites of mice after intense exercise on the treadmill. Race horses and humans became additional models for study.

Researchers from the Stanford University School of Medicine, Baylor College of Medicine, the University of California at Berkeley (USA), the University of Nijmegen named after St. Rudbod of Utrecht (Netherlands) and the University of Copenhagen (Denmark) have identified a metabolite – a small molecule – that is produced during exercise and effectively reduces appetite in overweight mice.

The benefits of exercise in protecting against obesity and associated cardiometabolic disease need not be reminded.

Meanwhile, lack of physical activity increases the risk of obesity, metabolic disorders and all-cause mortality, so in recent decades, interest in the search for “molecular transformers” that can mediate the benefits of playing sports has not subsided.

Previously, scientists have found specific signaling molecules (synthesized in a signaling cell to transmit a signal to another cell) that are regulated by exercise.

However, the extent to which these molecules act as important mediators – the so-called mediators – of training, remained not fully understood.

The authors of the new work set out to conduct a large-scale and unbiased assessment of circulating metabolites produced during exercise. To do this, they performed a metabolomic analysis of the blood of mice that ran on the track literally to the point of exhaustion.

“We found an increase in several metabolites, including lactate, fumarate, and succinate, which have previously been shown to be regulated by physical activity.

However, we discovered the metabolite most induced by exercise with the help of off-target metabolomics (metabolomics is a science that studies low molecular weight compounds, end products of metabolism. – Ed.).

It had a mass-to-charge ratio of 236.0928, corresponding to the chemical formula C12H14NO4. But such a molecule did not match the metabolite on our original target list,” the researchers said.

Therefore, they performed a targeted and non-targeted metabolomic analysis of the blood of Thoroughbred racehorses, which always demonstrate excellent athletic performance; samples were collected before and after the races. As a result, scientists identified the same molecule (mass-to-charge ratio – 236.0928).

“Fragmentation of this metabolite revealed a “daughter” ion with a mass-to-charge ratio of 88.040, corresponding to C3H6NO2.

Based on this, the original metabolite was tentatively assigned to Lac-Phe, an amidated conjugate of lactate and phenylalanine (that is, the molecule is synthesized from a by-product of intense physical activity responsible for a burning sensation in muscles (lactate) and an amino acid, one of the building blocks of proteins (phenylalanine).

Quantification of circulating Lac-Phe levels in mice and race horses revealed peak concentrations after exercise. Lac-Phe levels in the blood of mice increased significantly immediately after running and returned to baseline after an hour.

Lac-Phe, among other things, was found in many tissues of the body of rodents, but there their levels did not depend on running, ”the authors of the work explained.

Subsequent experiments showed that high doses of Lac-Phe for 12 hours suppressed appetite in obese rodents by about 50% compared to control groups, without affecting activity or energy expenditure.

When subjects were given Lac-Phe for ten days, they experienced weight loss (due to fat loss) and improved glucose tolerance. The effect appeared only after exercise, but not at rest, and only in overweight mice. Genetic elimination of Lac-Phe biosynthesis, on the other hand, made the animals eat more and made them more obese.

Humans were also included in a small part of the study. It turned out that when they were playing sports, the most dramatic increase in the levels of Lac-Phe in the blood caused sprint training.

In second place were strength exercises with weights, in third place were endurance exercises. Alas, the metabolic effects of Lac-Phe have not been evaluated in humans, so more research is needed.

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