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

Bruna B. Brandão, Søren Madsen, Atefeh Rabiee, Matteo Oliverio, Gabriel P. Ruiz, Danilo L. Ferrucci, Jéssica L. Branquinho, Daniela Razolli, Silas Pinto, Thomas S. Nielsen, William T. Festuccia, Adriano S. Martins, Beatriz A. Guerra, Thiago L. Knittel, Ditte Søgaard, Steen Larsen, Jørn W. Helge, Josef Brandauer, Lício A. Velloso, Brice EmanuelliJan Wilhelm Kornfeld, C. Ronald Kahn, Sara G. Vienberg, Juleen R. Zierath, Jonas T. Treebak, Marcelo A. Mori

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Abstract

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.

OriginalsprogEngelsk
TidsskriftPNAS
Vol/bind117
Udgave nummer38
Sider (fra-til)23932-23941
ISSN0027-8424
DOI
StatusUdgivet - 22. sep. 2020

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