The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans

FEBS J. 2014 Feb;281(3):739-49. doi: 10.1111/febs.12619. Epub 2013 Dec 10.


Irisin was first identified as a peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α) dependent myokine with the potential to induce murine brown-fat-like development of white adipose tissue. In humans, the regulatory effect of training on muscle FNDC5 mRNA expression and subsequently irisin levels in plasma is more controversial. We recruited 26 inactive men (13 normoglycaemic and normal weight, controls; and 13 slightly hyperglycaemic and overweight, pre-diabetes group) aged 40-65 years for a 12-week intervention of combined endurance and strength training with four sessions of training per week. Before and after the 12-week intervention period, participants were exposed to an acute endurance workload of 45 min at 70% of VO(2max), and muscle biopsies were taken prior to and after exercise. Skeletal muscle mRNA for PGC1A and FNDC5 correlated and both PGC1A and FNDC5 mRNA levels increased after 12 weeks of training in both control and pre-diabetes subjects. Circulating irisin was reduced in response to 12 weeks of training, and was increased acutely (~1.2-fold) just after acute exercise. Plasma concentration of irisin was higher in pre-diabetes subjects compared with controls. There was little effect of 12 weeks of training on selected browning genes in subcutaneous adipose tissue. UCP1 mRNA did not correlate with FNDC5 expression in subcutaneous adipose tissue or skeletal muscle or with irisin levels in plasma. We observed no enhancing effect of long-term training on circulating irisin levels, and little or no effect of training on browning of subcutaneous white adipose tissue in humans.

Keywords: FNDC5; PGC-1α; UCP1; exercise; irisin.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Exercise*
  • Fibronectins / blood
  • Fibronectins / genetics
  • Fibronectins / metabolism*
  • Humans
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Motor Activity
  • Muscle, Skeletal / metabolism*
  • Overweight / complications
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Physical Endurance
  • Pigments, Biological / genetics
  • Pigments, Biological / metabolism*
  • Prediabetic State / blood
  • Prediabetic State / complications
  • Prediabetic State / metabolism
  • Prediabetic State / therapy*
  • RNA, Messenger / metabolism
  • Resistance Training
  • Subcutaneous Fat, Abdominal / chemistry
  • Subcutaneous Fat, Abdominal / drug effects*
  • Subcutaneous Fat, Abdominal / metabolism
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Uncoupling Protein 1


  • FNDC5 protein, human
  • Fibronectins
  • Ion Channels
  • Mitochondrial Proteins
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Pigments, Biological
  • RNA, Messenger
  • Transcription Factors
  • UCP1 protein, human
  • Uncoupling Protein 1