Effects of physical activity on the link between PGC-1a and FNDC5 in muscle, circulating Ιrisin and UCP1 of white adipocytes in humans: A systematic review

Abstract

Exercise may activate a brown adipose-like phenotype in white Background: adipose tissue. The aim of this systematic review was to identify the effects of physical activity on the link between peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and fibronectin type III domain-containing protein 5 (FNDC5) in muscle, circulating Irisin and uncoupling protein one (UCP1) of white adipocytes in humans. Two Methods: databases (PubMed 1966 to 08/2016 and EMBASE 1974 to 08/2016 were searched using an appropriate algorithm. We included articles that examined physical activity and/or exercise in humans that met the following criteria: a) PGC-1a in conjunction with FNDC5 measurements, and b) FNDC5 and/or circulating Irisin and/or UCP1 levels in white adipocytes. We included Results: 51 studies (12 randomised controlled trials) with 2474 participants. Out of the 51 studies, 16 examined PGC-1a and FNDC5 in response to exercise, and only four found increases in both PGC-1a and FNDC5 mRNA and one showed increased FNDC5 mRNA. In total, 22 out of 45 studies that examined circulating Irisin in response to exercise showed increased concentrations when ELISA techniques were used; two studies also revealed increased Irisin levels measured via mass spectrometry. Three studies showed a positive association of circulating Irisin with physical activity levels. One study found no exercise effects on UCP1 mRNA in white adipocytes.The Conclusions: effects of physical activity on the link between PGC-1a, FNDC5 mRNA in muscle and UCP1 in white human adipocytes has attracted little scientific attention. Current methods for Irisin identification lack precision and, therefore, the existing evidence does not allow for conclusions to be made regarding Irisin responses to physical activity. We found a contrast between standardised review methods and accuracy of the measurements used. This should be considered in future systematic reviews.

Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes

“…The signalling pathways that control FNDC5 expression have not been fully elucidated with contradictory results from different in vitro studies [10,11]. For instance, it was reported that exercise-mimicking treatment failed to increase Fndc5 expression in myotubes [34].…”

“…Nevertheless, contradictory results were obtained from different laboratories that activation of PGC-1α and FNDC5 expressions were uncoupled in skeletal muscle during exercise [10]. In 2017, a meta-analysis including 51 studies reported that a solid conclusion could not be made about the link between PGC-1α activity and FNDC5 expression in response to physical activity [11]. Thus, the molecular mechanisms of exercise-regulated FNDC5 expression in skeletal muscle are still far from clear.…”

Eccentric resistance training and β-Hydroxy-β-methylbutyrate free acid affects muscle PGC-1α expression and serum irisin, nesfatin-1 and resistin

“…AMPK activation during exercise is one of the factors involved in increasing PGC-1α and irisin levels (Chavanelle et al, 2017). AMPK activation leads to the phosphorylation of PGC-1α as a modifier of FNDC5 and irisin secretion (Dinas et al, 2017). Also, PGC-1α activates PPARγ, which is involved in energy metabolism and stimulates increases in FNDC5 and irisin (Panati et al, 2016).…”

“…Exercise has numerous influences on multiple gut peptides and consequently energy balance (Dorling et al, 2018). Studies have investigated the effects of different modes of exercise training on PGC-1α (Dinas et al, 2017;Jung and Kim, 2014;Norheim et al, 2014), irisin (Dinas et al, 2017;Norheim et al, 2014;Samy et al, 2015), nesfatin-1 (Algul et al, 2017;Ghanbari Niaki et al, 2013b;Ghanbari-Niaki et al, 2010;Mogharnasi et al, 2018) and resistin (Cobbold, 2018;Shafiee and Sharifi, 2017;García-Hermoso et al, 2017). However, the effects of HMB on these factors have not been investigated widely.…”

Circulating molecules that control brown/beige adipocyte differentiation and thermogenic capacity

“…During cold exposure, irisin secretion is increased in a way proportional to shivering intensity, in magnitude similar to exercise‐stimulated secretion (Lee et al, ). Despite the mounting evidence, not all studies agree on the importance of irisin to exercise‐stimulated browning (Dinas et al, ), suggesting that more research needs to be performed in this field before any definite conclusion is made.…”