Abstract
A sexual dimorphism has been reported for the adipo-myokine irisin at rest and in response to exercise. The effects of male and female sex, adiposity, and gonadectomy on irisin secretion have not been investigated before. The objective of this study was to elucidate the effects of sex, adiposity, and gonadectomy in the regulation of irisin secretion as well as PGC-1α/FNDC5 mRNA and protein expression. We hypothesized that a lack of female sex hormones by ovariectomy reduces irisin levels and inhibits skeletal muscle expression of PGC-1α and FNDC5. Circulating irisin was measured in vivo in serum samples of healthy and obese men and women at rest and in response to acute exercise. The effects of gonadectomy on serum irisin, PGC-1α and FNDC5 muscle mRNA, and protein expression were investigated in ovariectomized (OVX) and orchiectomized (ORX) Wistar rats. Serum irisin at rest was not significantly different between men and women (lean or obese). However, in response to acute aerobic exercise, irisin levels increased significantly more in lean women versus men (p ≤ 0.05). In obese individuals, resting irisin concentrations were significantly higher compared to lean subjects (p ≤ 0.001) and the irisin response to acute exercise was blunted. Only the lack of gonadal hormones in OVX but not ORX rats increased serum irisin levels (p ≤ 0.01) and resulted in significantly increased body weight (p ≤ 0.01), adipose tissue content (p ≤ 0.05), muscle FNDC5 mRNA (p ≤ 0.05), and protein (p ≤ 0.01) expression without altering PGC-1α expression. Testosterone treatment in ORX rats leads to increased PGC-1α mRNA content and reduced PGC-1α protein content without affecting FDNC5 expression or serum irisin levels. We show that a sexual dimorphism exists for the acute irisin response to exercise in normal-weight but not in obese subjects. OVX, which is associated with increased adiposity and insulin insensitivity, increases basal FNDC5 expression and serum irisin, without altering PGC-1α expression. This may be an early sign for metabolic disturbances associated with menopause, such as a developing irisin resistance or an attempt of the organism to improve glucose metabolism.
Highlights
Maintaining energy homeostasis in response to metabolic perturbations is a major challenge for any multicellular and complex organism involving multiple and sometimes redundant physiological responses [1]
Our data reveal that there is a sexual dimorphism in the transient increase of irisin in response to acute, high-intensity endurance exercise: serum irisin concentrations were significantly higher immediately after intense endurance exercise in healthy, lean women versus men, suggesting that estrogens may play a role in the transient irisin
To elucidate the effects of gonadectomy on the signaling cascades leading to irisin concentrations, we investigated the effects of OVX/ORX on skeletal muscle PGC-1a and FNDC5 mRNA and protein levels
Summary
Maintaining energy homeostasis in response to metabolic perturbations is a major challenge for any multicellular and complex organism involving multiple and sometimes redundant physiological responses [1]. The novel adipo-myokine irisin was identified by Bostrom et al in a search for PGC-1a target genes coding for secreted proteins They identified the transmembrane protein FNDC5 (fibronectin [type 3] domain-containing [protein] 5) as a PGC-1a target, which is cleaved to produce soluble irisin. They later used adenoviral overexpression of FNDC5 in the liver of mice to show that transgenic mice exhibited enhanced oxygen consumption, increased amounts of white adipose tissue (WAT) browning, and improved glucose tolerance and insulin sensitivity [5]. In response to muscle contractions, AMPK and FNDC5 activation were abolished even though PGC-1a was increased in wild-type and knockout mice, suggesting that AMPK may be required for the regulation of FNDC5 independent of PGC-1a. The regulation and the physiological actions of irisin are not yet fully understood, and further studies are required to identify putative irisin receptors and study the underlying mechanisms responsible for activating FNDC5/irisin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
