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

Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23932-23941. doi: 10.1073/pnas.2011243117. Epub 2020 Sep 8.

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.

Keywords: adipose tissue; cross-talk; exercise; metabolic flexibility; microRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adaptation, Physiological / physiology
  • Adipocytes / metabolism
  • Adipose Tissue / metabolism*
  • Animals
  • Cells, Cultured
  • DEAD-box RNA Helicases / deficiency
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Exercise / physiology*
  • Female
  • Glycolysis
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Physical Conditioning, Animal
  • Ribonuclease III / deficiency
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism*

Substances

  • MIRN203 microRNA, human
  • MIRN203 microRNA, mouse
  • MicroRNAs
  • AMP-Activated Protein Kinases
  • DICER1 protein, human
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases