Posted on 19 October 2021
Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.
Why is this research important: Resistance training has well established health benefits including increasing muscle strength, reducing risk of sarcopenia, promoting fat loss and increasing insulin sensitivity. However, our understanding of exactly how mechanical loading of our muscles triggers some of these effects is somewhat patchy.
What did the researchers do: In this study, researchers brought about mechanical overload of the plantaris muscle in mice, which works to flex the ankle and knee joint. This was done by surgically removing a portion of the gastrocnemius muscle, which means the plantaris had to do more work. As a control, another group of mice underwent a sham surgery. They then measured and tracked the presence of extracellular vesicles in the mice’s blood. Extracellular vesicles (EVs) are lipid bilayer nanoparticles that are released by cells, and carry a cargo of signalling molecules like micro RNAs (molecules that can regulate gene expression by neutralising other RNA). Researchers hypothesised that this could be one way in which muscle cells signal to other tissues to bring about the health benefits of mechanical loading. The researchers also conducted similar measurements in healthy humans who underwent resistance training.
Key takeaway(s) from this research: Researchers found that after 3 days, mice in the experimental group showed about 70% decreased levels of micro RNAs in the plantaris muscle, while extracellular vesicles detected in the blood increased, suggesting that micro RNAs had been exported from the muscle cells by EVs. A similar effect was observed in humans who underwent resistance training.
Using fluorescent labelling, they were then able to observe where the EVs containing muscle-specific micro RNA went in the mice, and found that they were preferentially taken up by white adipose (fat) tissue, where their micro RNA cargo promoted the breakdown of fat (lipolysis). It did this by blocking Tfap2α, a factor that supresses the expression of adrenergic receptors. In this way, the EVs increased adrenergic signalling in the fat tissue, which resulted in increased fat breakdown.
All this seems to suggest that in response to mechanical loading, muscle cells signal to adipose tissue via EVs containing microRNA, resulting in increased adrenergic signalling and fat breakdown, at least in mice. The surgical procedure used here to induce mechanical loading is not very analogous to resistance exercise, since once the gastrocnemius is removed, the plantaris is continuously rather than sporadically loaded. However, the fact that EV release in response to training occurred in humans as well as mice hints at the possibility of a similar mechanism, though it probably works a little differently in humans. The specific adrenergic receptor of which the expression is affected – Adrβ3 – is not thought to be as important in human adipose tissue as it is in that of mice.
Mechanical overload-induced muscle-derived extracellular vesicles promote adipose tissue lipolysis: https://doi.org/10.1096/fj.202100242R
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