Only for fat
Scientists have found a molecule produced from exercise and suppressing appetite
Maria Azarova, Naked Science
A team of scientists conducted a comprehensive analysis of the metabolites of the blood of mice after intensive training on a treadmill. Additional models for the study were racehorses and people.
Staff of Stanford University Medical School, Baylor College of Medicine, University of California at Berkeley (USA), University of St. Radbod of Utrecht Nijmegen (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 study is published in the journal Nature (Li et al., An exercise-inducible metabolite that suppresses feeding and obesity).
There is no need to remind about the benefits of exercises that protect against obesity and related cardiometabolic diseases. Meanwhile, lack of physical activity increases the risk of obesity, metabolic disorders and mortality from all causes, therefore, in recent decades, interest in the search for "molecular converters" capable of mediating the benefits of sports has not subsided.
Previously, scientists have found specific signaling molecules (synthesized in a signaling cell to transmit a signal to another cell) regulated by physical exercise. However, the extent to which these molecules act as important mediators — the so—called mediators - of training has not been fully studied. The authors of the new work set out to conduct a large-scale and impartial assessment of circulating metabolites produced during exercise. To do this, they performed a metabolomic analysis of the blood of mice running on the track literally to exhaustion.
"We have identified an increase in the number of certain metabolites, including lactate, fumarate and succinate, which, as it turned out earlier, are regulated by physical activity. However, the metabolite most strongly induced by exercise, we found with the help of non—targeted metabolomics (metabolomics is a science that studies low-molecular compounds, the end products of metabolism. — Ed.). It had a mass-to-charge ratio of 236.0928, which corresponded to the chemical formula C12H14NO4. But such a molecule did not match the metabolite in our initial target list," the researchers said.
Therefore, they conducted a targeted and non-targeted metabolomic blood analysis of thoroughbred racehorses, which always demonstrate excellent athletic results; samples were collected before and after the races. As a result, scientists have identified the same molecule (the mass—to-charge ratio is 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 initial metabolite was previously assigned to Lac-Phe — amidated conjugate of lactate and phenylalanine (that is, the molecule is synthesized from a by—product of intense physical exertion, responsible for the burning sensation in the muscles (lactate), and amino acids - one of the building blocks of proteins (phenylalanine). — Ed.). <...> Quantitative determination of circulating Lac-Phe levels in mice and racehorses revealed peak concentrations after training. Lac-Phe levels in the blood of mice increased significantly immediately after running and returned to the baseline level an hour later. Lac-Phe, among other things, was detected in many tissues of the rodent body, but there their levels did not depend on running," the authors explained.
Subsequent experiments showed that high doses of Lac-Phe suppressed appetite in obese rodents for 12 hours — by about 50% compared to control groups, without affecting activity or energy consumption. When Lac-Phe was administered to the subjects for ten days, they experienced a decrease in body weight (due to fat loss) and improved glucose tolerance. The effect was manifested only after physical exercises, but not at rest, and exclusively in overweight mice. Genetic elimination of Lac-Phe biosynthesis, on the contrary, forced the animals to eat more and provoked obesity in them.
A small part of the study also involved people. It turned out that when they were doing sports, the most dramatic increase in Lac-Phe levels in the blood was caused by sprint training. In the second place were strength exercises with weights, in the third — endurance classes. Alas, scientists have not evaluated the metabolic effects of Lac-Phe on humans, so additional research will be required.
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