Science has confirmed that exercise stimulates specific areas of the brain to produce proteins that burn skeletal muscle fat

In a study published today in Science Advances, researchers from the State University of Campinas and the University of São Paulo in Brazil have for the first time characterized a neuromuscular circuit
that links skeletal muscle fat burning to proteins in the brain.
The study adds new evidence that regular exercise can help you lose weight and further underscores the importance of
exercise for health.

The hypothalamus is a brain region
that controls multiple functions.
Neuronal activity in the ventral medial (VMH) hypothalamus controls energy expenditure and skeletal muscle metabolism, including fatty acid oxidation and glucose metabolism
.

Interleukin-6 (IL-6) is a pro-inflammatory cytokine, but its central function plays a unique role in mammalian metabolism, such as burning skeletal muscle fat
.
Previous studies have shown that the ventral medial nucleus of the hypothalamus can alter muscle metabolism
when stimulated.
Hypothalamic IL6 is associated with
controlling energy and food consumption.
In obese rodents, exercise stimulates hypothalamic IL6 production to improve metabolic health
.

Previously, the team demonstrated that different types of acute exercise, such as swimming or treadmill running, can increase IL6 mRNA levels
in an animal's hypothalamus.
Now, they have proposed a new hypothesis that the production of IL6 in the hypothalamus may activate a neuromuscular circuit
that favors skeletal muscle fat burning.

In the new study, the researchers used an interaction plot of the human database of genotypic tissue expression from 81 individuals to show that there was a positive correlation between hypothalamic IL6 gene expression and lipid metabolism and mitochondria-related genes in skeletal muscle, and negatively correlated
with lipid biosynthesis-related genes.

The team then conducted a series of mouse experiments to demonstrate the presence of
neuromuscular circuits.
They observed a negative interaction
between hypothalamic Il6 gene expression and the expression of some lipid biosynthetic markers in mouse skeletal muscle.
After injection of IL6 in mouse brains, it increased oxygen consumption and stimulated key markers involved in fatty acid oxidation in soleus
muscle.
High levels of AMPK phosphorylation
are detected in the gastrocnemius muscle.

In another experiment, the researchers removed part of the sciatic nerve
on one leg of each mouse.
IL-6 is then injected into the animal brain
.
They observed that the mice had normal leg fat burning, but the other nerve was cut off in
the leg.
The experimental results show that the metabolism of skeletal muscle fat is only determined by the neural connections
between the hypothalamus and the muscles.

To elucidate how the nervous system ties up with muscles, the researchers used drugs to block the mice's α and β-adrenergic receptors
.
These two receptors are responsible for receiving nerve signals for muscles to perform functions
determined by the brain.

They found that blocking β-adrenergic receptors had little effect, but when blocking α-adrenergic receptors, muscle fat oxidation stopped or decreased sharply in mice
.

Computer simulations have shown that hypothalamic IL6 gene expression is closely related
to two subunits of muscle α-adrenergic receptors (adrenergic receptors α2A and α2C).
When IL-6 was injected into the brains of mice genetically engineered to produce these receptors, the results were verified: These mice had no metabolic activity
in muscle fat in their legs.

Finally, the researchers evaluated this neuromuscular circuit under physiological conditions (acute swimming) and confirmed that IL6 activates the ERK1/2 pathway in the ventral medial side of the hypothalamus, stimulating AMPK/ACC signaling and fatty acid oxidation
in mouse skeletal muscle.
Bioinformatics analysis showed that the hypothalamic IL6/ERK1/2 axis was closely related
to fatty acid oxidation and mitochondrial associated genes in hogeneic mouse and human skeletal muscle.

The team noted a link
between this neuromuscular circuit and fat oxidation that occurs after exercise stops.
This was once considered unimportant, but in fact, it can last for hours
.
Therefore, this neural circuit should be considered essential
for the weight loss process.

In conclusion, this study tells us that physical activity not only produces IL-6 in skeletal muscle, but also increases IL-6 levels in the hypothalamus, and the subsequent resulting fat burning in skeletal muscle may last much
longer than exercise itself.
The study highlights the importance of
physical exercise for weight loss interventions.

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