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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Bruna B Brandão
  • Søren Madsen
  • Matteo Oliverio
  • Gabriel P Ruiz
  • Danilo L Ferrucci
  • Jéssica L Branquinho
  • Daniela Razolli
  • Silas Pinto
  • William T Festuccia
  • Adriano S Martins
  • Beatriz A Guerra
  • Thiago L Knittel
  • Ditte Søgaard
  • Steen Larsen
  • Josef Brandauer
  • Lício A Velloso
  • Jan-Wilhelm Kornfeld
  • C Ronald Kahn
  • Sara G Vienberg
  • Marcelo A Mori

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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
ISSN0027-8424
DOIs
Publication statusE-pub ahead of print - 8 Sep 2020

ID: 248456875