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Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism

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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).

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Acknowledgements

Funding was provided by the University of New Mexico Research Grant, the University of New Mexico 2013–2014 College of Education Graduate Excellence Award, the University of New Mexico Summer 2012 Office of Graduate Studies Research, and the University of New Mexico Project and Travel Grant. We would like to devote a special thanks to Dr. Kristina Trujillo, and the University of New Mexico Department of Biochemistry and Molecular Biology for their assistance in this work. In addition, we would also like to thank the shared facilities available through the University of New Mexico Health Sciences Center.

Conflict of interest

The authors declare that they have no competing of interest.

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Authors and Affiliations

  1. Department of Exercise Science, High Point University, 833 Montlieu Ave., High Point, NC, 27268, USA

    Roger A. Vaughan

  2. Department of Health, Exercise and Sports Science, University of New Mexico, Albuquerque, NM, 87131, USA

    Roger A. Vaughan & Christine M. Mermier

  3. Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA

    Roger A. Vaughan & Nicholas P. Gannon

  4. Department of Individual, Family, and Community Education: Nutrition, University of New Mexico, Albuquerque, NM, 87131, USA

    Roger A. Vaughan & Carole A. Conn

  5. School of Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Nicholas P. Gannon

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  1. Roger A. Vaughan
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Correspondence to Roger A. Vaughan.

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Supplementary Figure 1

Glucose-Dependent PGC-1α Expression. Expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) following treatment with irisin at 12.4 ng/ml (+) or control (−) dissolved in media containing 50 %, 25 %, or 0 % normal glucose content. (TIFF 77 kb)

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Vaughan, R.A., Gannon, N.P., Mermier, C.M. et al. Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism. J Physiol Biochem 71, 679–689 (2015). https://doi.org/10.1007/s13105-015-0433-9

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