DICER is Necessary for the Metabolic Benefits of Exercise

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Exercise beneficially influences fat tissue metabolism, and researchers here find that the protein DICER is necessary for these benefits to take place. Expression of DICER declines with age, but is increased by structured exercise programs - though to a very variable degree. This variability suggests that a great deal more exploration is needed in order to understand this portion of the diverse set of mechanisms by which exercise improves health. DICER is just one part of a network of signals and regulators, and much is yet to be cataloged of their interactions.

Adipose tissue is not just a simple reservoir of energy for periods of food scarcity. It contributes significantly to regulation of the metabolism, releasing various molecules into the bloodstream, including microRNAs that modulate the expression of key genes in different parts of the organism, including the liver, pancreas, and muscles. Research has shown that both aging and obesity can impair the production of these regulatory microRNAs by adipose tissue and favor the development of diseases such as diabetes and dyslipidemia.

Results showed the occurrence of communication between muscle and adipose tissue during aerobic exercise via signaling molecules secreted into the bloodstream. This exchange of information makes energy consumption by adipose cells more efficient, enabling the metabolism to adapt to exercise and enhancing the performance of the muscles. Mice were subjected to a 60-minute treadmill running protocol for eight weeks. As they became fitter, treadmill speed and inclination were increased. At the end, in addition to the improvement in performance, the scientists found a significant elevation in adipocyte levels of DICER expression, which was accompanied by a reduction in body weight and visceral fat.

When they repeated the experiment with mice that were genetically modified not to express DICER in adipose cells, the researchers found that the beneficial effects of aerobic exercise were far smaller. "The animals didn't lose weight or visceral fat, and their overall fitness didn't improve. We also observed that adipose cells used the energy substrate differently in these GM mice than in wild mice, leaving less glucose available for muscles." In humans, six weeks of high-intensity interval training (HIIT) were sufficient to yield a fivefold increase in the amount of DICER in adipose tissue on average. The effect was observed in both younger volunteers, aged about 36, and older subjects, aged about 63. The response varied considerably between individuals, however, with DICER increasing as much as 25 times in some, and very little in others.

"We identified a molecule called miR-203-3p, whose expression increases with both training and caloric restriction. We showed that this microRNA is responsible for promoting metabolic adjustment in adipocytes. When muscles use up all their glycogen during prolonged exercise, molecular signals are sent to adipose tissue and miR-203-3p fine-tunes the adipocyte metabolism. We found this metabolic flexibility to be essential to good health as well as performance enhancement. In genetically modified mice that don't express DICER in adipocytes, this conversation between adipose tissue and muscles doesn't happen. It's a model that mimics aging and obesity. So when DICER declines, metabolic health is poor and degenerative processes accelerate."

Link: https://www.eurekalert.org/pub_releases/2020-12/fda-sdh120720.php

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source https://www.fightaging.org/archives/2020/12/dicer-is-necessary-for-the-metabolic-benefits-of-exercise/