Summary: Researchers identify a neuromuscular circuit that links muscle fat burning during physical exercise to protein action in the brain.
source: FAPESP
Article published in science progress Describes the neuromuscular circuit that links muscle fat burning to protein action in the brain.
The findings, obtained by researchers at the University of Campinas (UNICAMP) and the University of São Paulo (USP) in Brazil, contribute to a deeper understanding of how regular physical exercise can help you lose weight, reinforcing the habit’s importance for good health. .
“We set out to study the action of a protein called interleukin-6 [IL-6]It is a pro-inflammatory cytokine but performs various functions in some situations including exercise. In this case, the job is to burn muscle fat,” said Eduardo Ropelle, author of the recent article. Ropelle is a professor at UNICAMP’s Faculty of Applied Sciences (FCA) in Limeira and is supported by FAPESP.
The group led by Rubel actually observed in mice that oxidation of muscle fat began immediately in the legs when the protein was injected directly into the brain.
This part of the study was conducted while researching masters at Thayana Micheletti. She did part of the analysis during a research internship at the University of Santiago de Compostela in Spain.
The researchers analyzed the results to see if there was a neural circuit linking IL-6 production in the hypothalamus, a brain region that controls many functions, with the breakdown of skeletal muscle fat.
This part of the study was conducted in collaboration with Carlos Katashima, who is currently undergoing postdoctoral training in the Laboratory of Molecular Biology of Exercise (LaBMEx) of FCA-UNICAMP, headed by Ropelle.
Previous studies have shown that a specific part of the hypothalamus (central ventral nucleus) can alter muscle metabolism when stimulated. Upon discovering the presence of IL-6 receptors in this brain region, Brazilian researchers formulated the hypothesis that the protein produced there might activate a neuromuscular circuit that favors skeletal muscle fat burning.
Several experiments were performed to prove the existence of the circuit. In one, Katashima and colleagues removed a portion of the sciatic nerve in one leg of each rat. The sciatic nerve runs from the bottom of the spine to the feet.
When IL-6 was injected into the brain, fat was burned as expected in healthy legs but not in the leg with the severed nerve.
“Experiment showed that muscle fat is only metabolized thanks to the neural connection between the hypothalamus and the muscle,” Katashima said.
blocked receptors
To find out how the nervous system relates to muscles, the researchers administered drugs that block alpha- and beta-adrenergic receptors in mice, which in this case are responsible for receiving nerve signals to the muscles to perform the function determined by the brain.
Blocking the beta-adrenergic receptors had little effect, but muscle fat oxidation was halted or decreased sharply when the alpha-adrenergic receptors were blocked.
Computer simulations (in silico analysis) showed that hypothalamic IL-6 gene expression is closely associated with two subunits of muscle alpha-adrenergic receptors (alpha2A and alpha2C receptors).
When IL-6 was injected into the brains of mice genetically engineered to not produce these receptors, the results were validated: leg muscle fat was not metabolized in these mice.
An important finding of the study was the association between this neuromuscular circuit and post-burn, which is the oxidation of fat that occurs after exercise has ceased. This was considered minor, but in fact, it can last for hours and should be considered very important to the weight loss process.”
“We showed that physical exercise not only produces IL-6 in skeletal muscle, which was already known but also increases the amount of IL-6 in the hypothalamus,” Katashima noted.
The effects are therefore likely to last much longer than the duration of the exercise itself, underlining the importance of exercise for any anti-obesity intervention.
original search: open access.
“Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in controlling skeletal muscle metabolism” by Carlos Kiyoshi Katashima et al. science progress
Summary
Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in controlling skeletal muscle metabolism
Hypothalamic interleukin-6 (IL6) exerts extensive metabolic control.
Here, we show that IL6 activates the ERK1/2 pathway in the middle ventral hypothalamus (VMH), which stimulates AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle.
Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely related to fatty acid oxidation and mitochondrial-related genes in skeletal muscle of BXD homozygous mouse strains and humans.
We have shown that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modulate fatty acid metabolism in skeletal muscle.
To address the physiological significance of these findings, we showed that this neuromuscular circuit is required to support activation of AMPK/ACC signaling and fatty acid oxidation after exercise.
Finally, selective downregulation of the IL6 receptor in the VMH abolished the effects of exercise to maintain AMPK and ACC phosphorylation and fatty acid oxidation in muscle after exercise.
Together, these data demonstrated that the IL6/ERK axis in the VMH controls fatty acid metabolism in skeletal muscle.