Why You’re Not Losing Weight

If you’re struggling to lose weight despite exercising regularly, you’ll be happy to hear that new research may have solved the mystery.

It turns out you’re missing a key metabolic component that prevents you from burning fat during exercise. Plus, you may use less oxygen during exercise. In turn, you’re at risk for weight gain, which can lead to obesity and diabetes. The new study suggests there may be new ways to tackle obesity, beyond drugs that aim to curb appetite.

Researchers from Kobe University looked at a signaling molecule called PGC-1⍺ (“a”), which is involved in burning fat during exercise.

The body produces multiple versions of the protein, including so-called “b” and “c” versions. These two serve the same function as the “a” signaling molecule, with one major difference. The “b” and “c” versions are produced more than 10 times more in muscle during exercise. Meanwhile, version “a” does not show a similar increase.

Kobe University endocrinologist Ogawa Wataru and his team hypothesized that molecules “b” and “c” are responsible for energy metabolism during exercise. That is, they help you burn fat during exercise.

For the experiment, they created mice that lacked the signaling molecules “b” and “c” and only worked on the “a” variant. They then measured muscle growth, fat burning and oxygen consumption during three phases: rest, short-term exercise and long-term training.

In addition, they recruited human volunteers with and without type 2 diabetes for similar tests. People who are obese and those with type 2 diabetes may also have reduced levels of the signaling molecule.

The researchers concluded that mice lacking molecules “b” and “c” were unable to adapt quickly to short-term activities. As a result, they consumed less oxygen and burned less fat during and after exercise.

The scientists came to similar conclusions when they studied human volunteers. Both healthy subjects and those with type 2 diabetes used more oxygen and had less body fat when they produced more “b” and “c” proteins.

However, the study also found that long-term training may benefit subjects who only produce the “a” protein. The mic who trained regularly developed more muscle after six weeks of training, regardless of whether they could produce the “b” and “c” proteins.

Different versions of the signaling molecule PGC-1⍺ respond to different stimuli. The standard version (“a”) is produced in response to prolonged exercise, while the alternative versions (“b/c”) are produced in response to short-term exercise or exposure to cold. A deficiency of these versions makes it more difficult for affected individuals to respond to these stimuli by burning fat or building muscle mass.
Different versions of the signaling molecule PGC-1⍺ respond to different stimuli. The standard version (“a”) is produced in response to prolonged exercise, while the alternative versions (“b/c”) are produced in response to short-term exercise or exposure to cold. A lack of these versions makes it more difficult for affected individuals to respond to these stimuli by burning fat or building muscle mass. Image source: K. Nomura et al

Interestingly, the researchers discovered another important functionality of the PGC-1⍺ protein and its variants. It can influence the way subjects respond to cold.

This time, they looked at PGC-1⍺ changes in fat tissue. When exposed to cold, the mice produced more “b” and “c” proteins that help them burn fat to stay warm. The body temperature of the animals that couldn’t make “b” and “c” proteins dropped significantly when exposed to cold.

This finding suggests that the ‘b’ and ‘c’ versions of the signaling molecule can mediate metabolic responses in response to all kinds of short-term stimuli, not just exercise.

The main conclusion is that subjects can burn fat during and after exercise.

“Recently, anti-obesity drugs that suppress appetite have been developed and are increasingly prescribed in many countries around the world,” Ogawa and his team said in a statement.

“However, there are no drugs that treat obesity by increasing energy expenditure. If a compound can be found that increases the ‘b’ and ‘c’ versions, this could lead to the development of drugs that increase energy expenditure during exercise or even without exercise. Such drugs could potentially treat obesity independently of dietary restrictions.”

The full study is available in Molecular MetabolismThe researchers are now studying how proteins “b” and “c” increase in muscles during exercise.

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