The same workout produces different types of molecules that lead to different amounts of weight loss.

VALENCIA (EP) — ​​Some people lose weight more slowly than others while doing the same exercise, and a research team at Kobe University in Osaka, Japan, has found the reason. It’s well known that exercise burns fat, but for some people it’s much harder than for others, calling into question whether the mechanism for weight loss or gain is as simple as “fewer calories in than out.”

The researchers studied what happens to mice that fail to produce signaling molecules that specifically respond to short-term exercise and regulate the body’s energy metabolism. These mice consume less oxygen during exercise, burn less fat, and are therefore more likely to gain weight. Because the team found this link in humans, the new knowledge about this mechanism could help treat obesity.

Researchers have already identified a signaling molecule, a protein called PGC-1a, that appears to link exercise to its effects. However, it has not been possible to determine whether increasing the amount of this protein causes these effects or not, as some experiments suggested it and others did not.

More recently, Kobe University endocrinologist Ogawa Wataru and other researchers have discovered that there are actually several different versions of the protein. “These new versions of PGC-1a, called ‘b’ and ‘c,’ have almost the same function as the regular ‘a’ version, but during exercise, more than ten times more is produced in the muscles, whereas the a version doesn’t have that kind of increase,” Ogawa says.

So his team set out to demonstrate the idea that it was the newly discovered versions, rather than the previously known one, that regulated energy metabolism during exercise. To do this, the researchers created mice that lacked the b and c versions of the signaling molecule PGC-1a, although they had the standard a version, and measured muscle growth, fat burning, and oxygen consumption in the mice during resting, short-term, and long-term exercise. They also recruited people with and without type 2 diabetes and subjected them to tests similar to those in the mice, since people with insulin intolerance and obesity are known to have reduced levels of the signaling molecule.

Ogawa and his team published their results in the journal. Molecular metabolism. They found that while all versions of the signaling molecule trigger similar biological responses, different levels of their production have far-reaching consequences for the body’s health. The lack of alternative b and c versions of PGC-1a means that the body is essentially blind to short-term activity and does not adapt to these stimuli, causing such people to consume less oxygen and burn less fat during and after exercise. , training.

In humans, the research team found that the more subjects produced versions of the b and c signaling molecule, the more oxygen they consumed and the lower their body fat percentage, both in healthy people and in people with type 2 diabetes. Therefore, the hypothesis that genes in skeletal muscle determine susceptibility to obesity was correct, Ogawa summarizes these findings.

However, they also found that long-term exercise stimulated production of the standard version of PGC-1a, and mice that exercised regularly for six weeks experienced increases in muscle mass regardless of whether they were able to produce standard versions of the alternative signaling molecule or not.

In addition to production in muscle, the Kobe University team looked at how the production of different versions of PGC-1a changed in fat tissue and found no corresponding effect in response to exercise. However, because animals also burn fat to maintain body temperature, the researchers also looked at the mice’s ability to tolerate cold. Indeed, they found that production of versions b and c of the signaling molecule in brown fat tissue increased when the animals were exposed to cold, and that the body temperature of individuals who couldn’t produce these versions dropped significantly under these conditions.

On the one hand, this may contribute to the increase in body fat in these people, but on the other hand, it seems to mean that the B and C versions of the signaling molecule may be responsible for metabolic adaptation to short-term stimuli more generally.

Drugs are being sought that improve energy expenditure.

Ogawa and his team note that understanding the physiological activity of different versions of PGC-1a may allow for the development of treatment strategies for obesity. Anti-obesity drugs that suppress appetite have recently been developed and are increasingly prescribed in many countries. However, there are no drugs that treat obesity by increasing energy expenditure.

“If a substance is found that increases the amount of versions B and C, it could lead to the development of drugs that improve energy expenditure during exercise or even without it. These drugs could treat obesity regardless of dietary restrictions,” he warns.

The team is currently conducting research to learn more about the mechanisms that lead to increased production of versions b and c of the signaling molecule during exercise.