Science Advances: How physical exercise burns muscle fat

An article describes for the first time a neuromuscular circuit that links
the burning of muscle fat to the activity of a protein in the brain.

The findings obtained by researchers from the State University of Campinas (UNICAMP) and the Söo Paul University (USP) in Brazil contribute to a deeper understanding of how regular physical activity can contribute to weight loss and reinforce the importance of
this habit for health.

"We set out to study the role of
a protein called interleukin 6.
IL-6 is a pro-inflammatory cytokine but performs different functions
in some situations, including exercise.
In this case, its function is to burn muscle fat
.

The team led by Ropelle has observed in mice that muscle fat immediately begins to oxidize
in the legs when the protein is injected directly into the brain.
This part of the research was conducted
during the master's studies of Thayana Micheletti, who was awarded a FAPESP scholarship.

The researchers analyzed the results to determine if there is a neural circuit that links
IL-6 production in the hypothalamus to the breakdown of skeletal muscle fat.
The hypothalamus is an area of the brain that controls a variety of functions
.
This part of the research was carried out in collaboration with Carlos Katashima, who is currently doing a postdoctoral internship at FCA-UNICAMP's Sports Molecular Biology Laboratory (LaBMEx), led
by Ropelle.

Previous research has shown that when stimulated, specific parts of the hypothalamus (ventromedial nucleus) can alter muscle metabolism
.
After detecting the presence of IL-6 receptors in brain regions, Brazilian researchers proposed a hypothesis that proteins produced there may activate a neuromuscular circuit that favors skeletal muscle fat burning
.

To prove the existence of such a circuit, several experiments
were carried out.
In one of the studies, Katashima and his colleagues removed part of the sciatic nerve
on one leg of each mouse.
The sciatic nerve extends from the lower part of the spine to the
feet.

When IL-6 is injected into the brain, normal leg fat is burned, but not in legs where nerves are
severed.
"Experiments have shown that muscle fat metabolism is only due to the neural connections
between the hypothalamus and muscles," Katashima said.

Block receptors

To find out how the nervous system is linked to muscles, the researchers used drugs to block mice's — and adrenergic receptors, in this case receptors responsible for receiving nerve signals for muscles to perform functions
determined by the brain.

Blockade-adrenergic receptors have little effect, but when blocking - adrenergic receptors, oxidation of muscle fat stops or sharply decreases
.

In vivo simulations (silicon analysis) showed that hypothalamic IL-6 gene expression was strongly associated
with two muscle α-adrenergic receptor sub-adrenal receptors alpha2A and alpha2C.
When IL-6 was injected into the brains of mice genetically engineered not to produce these receptors, the results were validated: the muscle fat in the legs of these mice was not metabolized
.

"An important finding of this study is the link between neuromuscular circuits and aftercombustion, which is the oxidation of
fat that occurs after motor stops.
This has always been considered secondary, but the fact that it can last for several hours should be considered vital in the weight loss process," Ropelle said
.

"We found that physical activity not only produces IL-6 in skeletal muscle, which is known, but also increases the amount
of IL-6 in the hypothalamus," Katashima noted.
"As a result, this effect is likely to last much longer than the duration of exercise itself, underlining the importance of
exercise for any intervention to combat obesity.
"

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