Overview: Researchers have identified a neuromuscular circuit that links the burning of muscle fat during exercise to the actions of proteins in the brain.
sauce: FAPESP
Articles published in scientific progress It describes the neuromuscular circuits that link the burning of muscle fat to the actions of proteins in the brain.
Findings obtained in Brazil by researchers at the University of Campinas (UNICAMP) and the University of São Paulo (USP) contribute to a better understanding of how regular exercise can help with weight loss, and how this practice can help health. reinforces the importance of .
“We set out to study the action of a protein called interleukin-6. [IL-6]which is an inflammatory cytokine, but serves a different function in some situations, including exercise. Ropelle is a professor at the Faculty of Applied Sciences (FCA) at UNICAMP in Limeira and is supported by FAPESP.
A group led by Ropelle had already observed in mice that when protein was injected directly into the brain, muscle fat oxidation began immediately in the legs.
This part of the research was done during Thayana Micheletti’s master’s work. She performed some of her analyzes during her research internship at her University of Santiago de Compostela, Spain.
The researchers analyzed the results to see if there is a neural circuit linking the production of IL-6 in the hypothalamus, a brain region that controls several functions, and the breakdown of skeletal muscle fat.
This part of the study was carried out in collaboration with Carlos Katashima, a postdoctoral intern at FCA-UNICAMP’s Laboratory of Exercise and Molecular Biology (LaBMEx), led by Ropelle.
Previous studies have shown that specific parts of the hypothalamus (ventromedial nucleus) can alter muscle metabolism when stimulated. Brazilian researchers who detected the presence of his IL-6 receptors in this brain region suggested that proteins produced there could activate neuromuscular circuits that promote the burning of skeletal muscle fat. I made a hypothesis.
Several experiments were performed to demonstrate the existence of the circuit. For one, Katashima and his colleagues excised a portion of the sciatic nerve in one leg of each mouse, which runs from the bottom of the spine to the foot.
Injecting IL-6 into the brain burned fat as expected in the intact leg, but not in the nerve-severed leg.
“Experiments have shown that muscle fat is metabolized thanks to the neural connections between the hypothalamus and muscle,” Katashima said.
blocked receptor
To find out how the nervous system is connected to muscles, researchers administered drugs that block alpha and beta adrenergic receptors in mice.
Blocking beta-adrenergic receptors had little effect, but when alpha-adrenergic receptors were blocked, muscle fat oxidation was halted or greatly reduced.
Computer simulations (in silico analysis) showed that hypothalamic IL-6 gene expression is strongly correlated with two muscle alpha-adrenergic receptor subunits (adrenergic receptors alpha2A and alpha2C).
Injecting IL-6 into the brains of mice genetically engineered not to produce these receptors validated the results. Leg muscle fat was not metabolized in these mice.
“A key finding of this study was the link between this neuromuscular circuit and afterburn, the oxidation of fat that occurs after exercise has ended. It can last for hours and should be considered very important to the weight loss process.
“We have shown that physical exercise is not only already known to produce IL-6 in skeletal muscle, but also increases the amount of IL-6 in the hypothalamus.
“The effects are therefore likely to last much longer than the duration of exercise itself, underscoring the importance of exercise for interventions against obesity.”
About this exercise and neuroscience research news
author: press office
sauce: FAPESP
contact: Press Office – FAPESP
image: Image credit goes to Eduardo Ropelle/FCA-UNICAMP
See also
Original research: open access.
“Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism]Carlos Kiyoshi Katashima and others scientific progress
Overview
Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism
Hypothalamic interleukin 6 (IL6) exerts extensive metabolic regulation.
Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH) and stimulates AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle.
Bioinformatic analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation- and mitochondria-related genes in isogenic BXD mouse strains and human skeletal muscle.
We have shown that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to alter fatty acid skeletal muscle metabolism.
To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to support AMPK/ACC signaling activation and fatty acid oxidation after exercise.
Finally, selective downregulation of IL6 receptors in VMH abolished the effects of exercise on maintaining AMPK and ACC phosphorylation and fatty acid oxidation in muscle after exercise.
Taken together, these data indicate that the IL6/ERK axis in VMH controls fatty acid metabolism in skeletal muscle.
