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

Abstract

Irisin was first identified as a peroxisome proliferator-activated receptor c co-activator-1a (PGC-1a) 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.

Irisin and FNDC5: effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women

“…In this regard, it is necessary to note that we did not control for food-intake and hence no conclusive inferences can be made. However, such a tentative lack of an effect of irisin on fat mass is supported by studies such as Raschke et al (2013) who did not find an effect of irisin on browning of cultured human adipocytes and Norheim et al (2014) who did not find an association between s-irisin and markers of browning in subcutaneous adipocytes in human subjects. Still, a role for irisin in browning of adipocytes in human subjects cannot be ruled out.…”

“…Still, a role for irisin in browning of adipocytes in human subjects cannot be ruled out. Different deposits of human adipocyte have been shown to respond differently to irisin exposure (Lee et al 2014), which may indicate that the negative results presented by Raschke et al (2013) and Norheim et al (2014) was an artefact of adipocyte sampling.…”

“…In contrast to these negative findings, several studies also seem to suggest that irisin is a training-responsive myokine in humans (Huh et al 2012;Kraemer et al 2013;Norheim et al 2014; Lee et al 2014). These aberrances may of course be caused by per-chance statistical errors or technical flaws, perhaps related to dubious quantification of s-irisin (Raschke et al 2013;Erickson 2013).…”

Increased FNDC5 is associated with insulin resistance in high fat-fed mice

“…2014; Norheim et al. 2014) in humans and animals. Exercise‐induced expression of FNDC5/irisin in muscle has been shown to be dependent on increased PGC‐1 α (Bostrom et al.…”

“…demonstrated that combined chronic endurance and resistance training increased both PGC‐1 α and FNDC5 skeletal muscle mRNA, whereas circulating irisin increased only in response to acute combined endurance and resistance exercise (Norheim et al. 2014). Further study is needed to differentiate the effects of acute and chronic exercise on FNDC5 and irisin.…”