Dynamic changes in DICER levels in adipose tissue control metabolic adaptations to exercise
Bruna B. Brandão, Søren Madsen, Atefeh Rabiee, Matteo Oliverio, Gabriel Palermo Ruiz, Danilo Lopes Ferrucci, Jéssica Branquinho, Daniela S. Razolli, Silas Pinto, Thomas S. Nielsen, William T. Festuccia, Adriano S. Martins, Beatriz Alves Guerra, Thiago L. Knittel, Ditte Søgaard, Steen Larsen, Jørn Wulff Helge, Josef Brandauer, Lı́cio A. Velloso, Brice Emanuelli, Jan‐Wilhelm Kornfeld, C. Ronald Kahn, Sara G. Vienberg, Juleen R. Zierath, Jonas T. Treebak, Marcelo A. Mori
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.