Dynamic changes in DICER levels in adipose tissue control metabolic adaptations to exercise

Dynamic changes in DICER levels in adipose tissue control metabolic adaptations to exercise
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DOI:
10.1073/pnas.2011243117
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发表时间:
2020-09-22
影响因子:
11.1
通讯作者:
Mori, Marcelo A.
Mori, Marcelo A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Brandao, Bruna B.;Madsen, Soren;Mori, Marcelo A.

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DICER 是 microRNA (miRNA) 生物合成中的关键酶。在这里,我们发现有氧运动训练可以上调小鼠和人类脂肪组织中的 DICER。这可以通过将运动小鼠的血清输注到久坐的小鼠中来模拟,并且依赖于肌肉和脂肪细胞中 AMPK 介导的信号传导。脂肪细胞 DICER 是全身代谢适应有氧运动训练所必需的,部分原因是通过控制脂肪组织中的底物利用,从而支持骨骼肌功能。运动训练增加了脂肪组织中的总体 miRNA 表达,并且 miR-203-3p 的上调限制了代谢应激条件下脂肪中的糖酵解。我们认为运动训练诱导的脂肪细胞中 DICER-miR-203-3p 上调是协调来自工作肌肉的信号以促进全身代谢适应的关键适应性反应。
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.