title: The role of sex, adiposity, and gonadectomy in the regulation of irisin secretion.
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.
authors.affiliation: Division of Sports Medicine, Department of Internal Medicine, University Hospital Ulm, Parkstr. 11, 89075, Ulm, Germany. martina.zuegel@uniklinik-ulm.de.
authors.forename: M
authors.initials: M
authors.lastname: Zügel
authors.affiliation: Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Division of Sports Medicine, Department of Internal Medicine, University Hospital Ulm, Parkstr. 11, 89075, Ulm, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Laszlo
authors.affiliation: Department of Health Sciences and Sports Medicine, University of Physical Education, Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Bosnyák
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sports University Cologne, Cologne, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Weigt
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sports University Cologne, Cologne, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Müller
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sports University Cologne, Cologne, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Diel
authors.affiliation: Division of Sports Medicine, Department of Internal Medicine, University Hospital Ulm, Parkstr. 11, 89075, Ulm, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Steinacker
authors.affiliation: Division of Sports Medicine, Department of Internal Medicine, University Hospital Ulm, Parkstr. 11, 89075, Ulm, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schumann
mesh_terms: D050154:Adiposity / Q000187:drug effects / Q000502:physiology*; D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000097:blood*; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D043343:Testosterone Propionate / Q000494:pharmacology; D055815:Young Adult
chemical_list: C583676:FNDC5 protein, rat; D005353:Fibronectins; D043343:Testosterone Propionate
keywords: FNDC5; Irisin; Obesity; Orchiectomy; Ovariectomy; PGC-1α; Sex hormones; Skeletal muscle