Study shows how exercise burns muscle fat

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

The results, obtained by researchers from the State University of Campinas (UNICAMP) and the University of São Paulo (USP) in Brazil, contribute to a deeper understanding of how regular physical activity contributes to weight loss and underscore the importance of this habit for a good health .

“We wanted to investigate the effect of a protein called interleukin 6 [IL-6], which is a pro-inflammatory cytokine but has other functions in some situations, including exercise. In this case, the function is to burn muscle fat,” he said Edward Ropole, last author of the article. Ropelle is a Professor at UNICAMP’s School of Applied Sciences (FCA) in Limeira and is powered by FAPESP.

Ropelle’s group had already observed in mice that muscle fat oxidation started immediately in the legs when the protein was injected directly into the brain. This part of the study was carried out during the master’s degree Thayana Michelettiwith a Scholarship from FAPESP.

Micheletti performed 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 is a neural circuit that links the production of IL-6 in the hypothalamus, a brain region that controls multiple functions, to the breakdown of skeletal muscle fat. This part of the study was conducted in collaboration with Carlos Katashimawho is currently on one Postdoctoral internship at FCA-UNICAMP’s Laboratory of Molecular Biology of Exercise (LaBMEx) under the supervision of Ropelle.

Previous studies showed that a specific part of the hypothalamus (the ventromedial nucleus) could alter muscle metabolism when stimulated. Upon demonstrating the presence of IL-6 receptors in this brain region, Brazilian researchers hypothesized that the protein produced there might activate a neuromuscular circuit that promotes the burning of skeletal muscle fat.

Several experiments were performed to demonstrate the existence of the circuit. In one case, Katashima and colleagues removed part of the sciatic nerve in one of each mouse’s legs. The sciatic nerve runs from the lower spine to the feet.

When IL-6 was injected into the brain, fat was burned in the intact legs, as expected, but not in the leg with the severed nerve. “The experiment showed that muscle fat is only metabolized thanks to the nerve connection between the hypothalamus and muscle,” Katashima said.

Blocked receptors

To find out how the nervous system is connected to the muscles, the researchers administered drugs that blocked the mice’s alpha- and beta-adrenergic receptors, which in this case are responsible for receiving nerve signals, allowing the muscles to function as directed by the brain carry out.

Blocking the beta-adrenergic receptors had little effect, but muscle fat oxidation stopped or was greatly reduced when the alpha-adrenergic receptors were blocked.

Computer simulations (in silico analysis) showed that hypothalamic IL-6 gene expression was strongly correlated with two muscle alpha-adrenergic receptor subunits (adrenoceptors alpha2A and alpha2C). When IL-6 was injected into the brains of mice that had been genetically engineered not to produce these receptors, the results were validated: leg muscle fat was not metabolized in these mice.

“A key finding of the study was the association between this neuromuscular circuitry and afterburn, a fat oxidation that occurs after exercise has stopped. This was considered secondary, but in fact it can take hours and should be considered extremely important to the weight loss process,” Ropelle said.

“We have shown that exercise not only produces IL-6 in skeletal muscle, which was already known, but also increases the amount of IL-6 in the hypothalamus,” noted Katashima. “It is therefore likely that the effects last much longer than the duration of the exercise itself, underscoring the importance of exercise in any anti-obesity intervention.”

FAPESP also supported the study through a Thematic project lead by Adelino Sanchez Ramos da SilvaCo-author of the article and Professor at the Ribeirão Preto School of Physical Education and Sport (EEFERP-USP).

About the Sao Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public body with a mission to support scientific research in all fields of knowledge by awarding grants, fellowships and grants to researchers affiliated with universities and research institutions in the state of São Paulo, Brazil . FAPESP recognizes that the very best research can only be achieved by collaborating with the best researchers at the international level. Therefore, it has established partnerships with funding agencies, universities, private companies and research institutes in other countries known for the quality of their research, and has encouraged scientists funded by its fellowships to further develop their international collaborations. You can learn more about FAPESP at www.fapesp.br/en and visit the FAPESP news agency at www.agencia.fapesp.br/en to keep up to date with the latest scientific breakthroughs that FAPESP is making through its many programs, Awards and research centers supported. You can also subscribe to the FAPESP news agency at http://agencia.fapesp.br/subscribe