title: Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism.
abstract: Exercise offers several benefits for health, including increased lean body mass and heightened energy expenditure, which may be partially attributable to secretory factors known as myokines. Irisin, a recently identified myokine, was shown to increase metabolic rate and mitochondrial content in both myocytes and adipocytes; however, the mechanism(s) of action still remain largely unexplained. This work investigated if irisin functions by acting as an inflammatory myokine leading to cellular stress and energy expenditure. C2C12 myotubes were treated with various concentrations of irisin, TNFα, or IL6 for various durations. Glycolytic and oxidative metabolism, as well as mitochondrial uncoupling, were quantified by measurement of acidification and oxygen consumption, respectively. Metabolic gene and protein expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting, respectively. Mitochondrial content was assessed by fluorescent imaging. NFκB activity was assessed using an NFκB GFP-linked reporter system. Consistent with previous findings, irisin significantly increased expression of several genes including peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) leading to increased mitochondrial content and oxygen consumption. Despite some similarities between TNFα and irisin treatment, irisin failed to activate the NFκB pathway like TNFα, suggesting that irisin may not act as an inflammatory signal. Irisin has several effects on myotube metabolism which appear to be dependent on substrate availability; however, the precise mechanism(s) by which irisin functions in skeletal muscle remain unclear. Our observations support the hypothesis that irisin does not function through inflammatory NFκB activation like other myokines (such as TNFα).
authors.affiliation: Department of Exercise Science, High Point University, 833 Montlieu Ave., High Point, NC, 27268, USA. rvaughan@highpoint.edu.|Department of Health, Exercise and Sports Science, University of New Mexico, Albuquerque, NM, 87131, USA. rvaughan@highpoint.edu.|Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA. rvaughan@highpoint.edu.|Department of Individual, Family, and Community Education: Nutrition, University of New Mexico, Albuquerque, NM, 87131, USA. rvaughan@highpoint.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Vaughan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA. ngannon@mcw.edu.|School of Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. ngannon@mcw.edu.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Gannon
authors.affiliation: Department of Health, Exercise and Sports Science, University of New Mexico, Albuquerque, NM, 87131, USA. cmermier@unm.edu.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Mermier
authors.affiliation: Department of Individual, Family, and Community Education: Nutrition, University of New Mexico, Albuquerque, NM, 87131, USA. cconn@unm.edu.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Conn
mesh_terms: D000818:Animals; D002460:Cell Line; D005353:Fibronectins / Q000502:physiology*; D015870:Gene Expression; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010101:Oxygen Consumption
chemical_list: C571428:FNDC5 protein, mouse; D005353:Fibronectins; D016328:NF-kappa B
keywords: Fibronectin type III domain containing protein 5 (FNDC5); Interleukin 6 (IL6); Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α); Secretome; Tumor necrosis factor α (TNFα)