Program in Molecular Biology, Federal University of São Paulo, 04044-020 São Paulo, Brazil.
Department of Biophysics, Federal University of São Paulo, 04023-062 São Paulo, Brazil.
Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23932-23941. doi: 10.1073/pnas.2011243117. Epub 2020 Sep 8.
DICER is a key enzyme in microRNA (miRNA) biogenesis. Here we show that aerobic exercise training up-regulates DICER in adipose tissue of mice and humans. This can be mimicked by infusion of serum from exercised mice into sedentary mice and depends on AMPK-mediated signaling in both muscle and adipocytes. Adipocyte DICER is required for whole-body metabolic adaptations to aerobic exercise training, in part, by allowing controlled substrate utilization in adipose tissue, which, in turn, supports skeletal muscle function. Exercise training increases overall miRNA expression in adipose tissue, and up-regulation of miR-203-3p limits glycolysis in adipose under conditions of metabolic stress. We propose that exercise training-induced DICER-miR-203-3p up-regulation in adipocytes is a key adaptive response that coordinates signals from working muscle to promote whole-body metabolic adaptations.
DICER 是 microRNA（miRNA）生物发生的关键酶。在这里，我们表明，有氧运动训练可上调小鼠和人类脂肪组织中的 DICER。将运动小鼠的血清输注到久坐不动的小鼠中可以模拟这种情况，这取决于肌肉和脂肪细胞中 AMPK 介导的信号。脂肪细胞 DICER 是适应有氧运动训练的全身代谢适应所必需的，部分原因是它允许脂肪组织中受控的底物利用，这反过来又支持骨骼肌功能。运动训练增加了脂肪组织中整体 miRNA 的表达，而 miR-203-3p 的上调可在代谢应激条件下限制脂肪组织中的糖酵解。我们提出，运动训练诱导的脂肪细胞中 DICER-miR-203-3p 的上调是一种关键的适应性反应，可协调来自工作肌肉的信号，以促进全身代谢适应。
