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Irisin and FNDC5: effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women

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Abstract

Purpose

To investigate the effects of strength training on abundances of irisin-related biomarkers in skeletal muscle and blood of untrained young women, and their associations with body mass composition, muscle phenotype and levels of thyroid hormones.

Methods

Eighteen untrained women performed 12 weeks of progressive whole-body heavy strength training, with measurement of strength, body composition, expression of irisin-related genes (FNDC5 and PGC1α) in two different skeletal muscles, and levels of serum-irisin and -thyroid hormones, before and after the training intervention.

Results

The strength training intervention did not result in changes in serum-irisin or muscle FNDC5 expression, despite considerable effects on strength, lean body mass (LBM) and skeletal muscle phenotype. Our data indicate that training affects irisin biology in a LBM-dependent manner. However, no association was found between steady-state serum-irisin or training-associated changes in serum-irisin and alterations in body composition. FNDC5 expression was higher in m.Biceps brachii than in m.Vastus lateralis, with individual expression levels being closely correlated, suggesting a systemic mode of transcriptional regulation. In pre-biopsies, FNDC5 expression was correlated with proportions of aerobic muscle fibers, a relationship that disappeared in post-biopsies. No association was found between serum-thyroid hormones and FNDC5 expression or serum-irisin.

Conclusion

No evidence was found for an effect of strength training on irisin biology in untrained women, though indications were found for a complex interrelationship between irisin, body mass composition and muscle phenotype. FNDC5 expression was closely associated with muscle fiber composition in untrained muscle.

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Notes

  1. Throughout the manuscript, the term “steady-state” refers to gene expression/hormone abundance measured in biological material sampled at rest (in this study: >48 h since last training session).

Abbreviations

18S rRNA:

18S ribosomal RNA

β2m:

β2-Microglobulin

β-a:

β-Actin

BB:

musculus Biceps brachii

DXA:

Dual-energy X-ray absorptiometry

EIA:

Enzyme immunoassay

FM:

Fat mass

FNDC5:

Fibronectin type III domain-containing protein 5

FT3:

Free triiodothyronine

FT4:

Free thyroxine

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

LBM:

Lean body mass

MyHC:

Myosin heavy chain

PGC1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

PolR2A:

Polymerase (RNA) II (DNA directed) polypeptide A

PPIA:

Peptidylprolyl isomerase A (cyclophilin A)

qRT-PCR:

Quantitative reverse transcriptase-polymerase chain reaction

RM:

Repetition maximum

RPL32:

Ribosomal protein L32 (RPL32)

s-irisin:

Serum concentrations of irisin

TBP:

TATA box binding protein

TSH:

Thyroid-stimulating hormone

UBC:

Ubiquitin C

VL:

musculus Vastus lateralis

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Acknowledgements

This study was supported by grants 203961 and 222717 to SE from the Regional Science Fund—Innlandet, Norway. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Thanks to Daniel Hammarström for valuable assistance with statistical analyses. Thanks to students Øyvind Skattebo, Knut Sindre Mølmen, Thomas Fenne, Fredrik Lie Haugen, Amund Løvstad, Trine C. Larsen, Gunnar Disch, Eirik F. Langøy and Elisabeth Hildenes for assistance during intervention follow-up and data sampling.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Lillehammer University College, P.O. Box 952, 2604, Lillehammer, Norway

    S. Ellefsen, O. Vikmoen, G. Slettaløkken, H. Nygaard, G. Vegge & B. R. Rønnestad

  2. Innlandet Hospital Trust, Lillehammer, Norway

    J. E. Whist, I. Rauk & T. A. Strand

  3. Hospital for Rheumatic Diseases, Lillehammer, Norway

    I. Hollan

  4. Norwegian School of Sport Science, Oslo, Norway

    T. Raastad

Authors
  1. S. Ellefsen
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  2. O. Vikmoen
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  3. G. Slettaløkken
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  4. J. E. Whist
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  5. H. Nygaard
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  6. I. Hollan
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  7. I. Rauk
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  8. G. Vegge
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  9. T. A. Strand
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  10. T. Raastad
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  11. B. R. Rønnestad
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Corresponding author

Correspondence to S. Ellefsen.

Additional information

Communicated by Martin Flueck.

S. Ellefsen, O. Vikmoen, G. Slettaløkken, JE. Whist, H. Nygaard, I. Hollan, I. Rauk, G. Vegge, TA. Strand and BR. Rønnestad member of The Lillehammer Research Center for Medicine and Exercise Physiology.

Electronic supplementary material

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Supplementary material 1 (DOCX 15 kb)

421_2014_2922_MOESM2_ESM.tif

Figure s1. Expression stability (M) of nine selected reference genes in A) musculus Vastus lateralis (VL) and B) musculus Biceps brachii (BB) following 12 wks of strength training in 17 previously untrained women. M was calculated using GeNorm, as described by Vandesompele et al. (2002). In both VL and BB, B2m and PPIA were found to be the most stably expressed reference genes, ranking them as most suitable for normalization of target gene qRT-PCR data. (TIFF 227 kb)

421_2014_2922_MOESM3_ESM.tif

Figure s2. Per-mg-tissue expression of PPIA in untrained (pre, black columns) and trained (post, white columns) musculus Vastus lateralis (VL) and musculus Biceps brachii (BB). Data were normalized to the external reference gene mw2060, an approach developed by Ellefsen et al. (2008). The effect of training on gene expression was tested using a paired t test. No differences were found between groups. Values are mean ± S.D. (TIFF 72 kb)

421_2014_2922_MOESM4_ESM.tif

Figure s3. Effects of 12 weeks of progressive heavy strength training on steady-state expression of FNDC5, PGC1α splice variants 1 and 4 (s1 and s4), TBP, GAPDH and MyHC2X in A, C) musculus Vastus lateralis (VL) and B, D) musculus Biceps brachii (BB) of 17 previously untrained young women. Strength training was performed as either 3L1U (three sets lower body - one set upper body; n = 7; in A-B) or 1L3U (one set lower body - three sets upper body; n = 10; in C-D). Muscle biopsies were sampled before (pre) and after (post) the training period. Data were normalized to PPIA and are presented as post-training expression relative to pre-training expression, measured as log2-fold change. Effects of training on gene expression were tested on log2-transformed data using paired t tests. * = p<0.05, *** = p<0.001. Data are presented as box plots, with the central line marking the data set median.(TIFF 742 kb)

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Ellefsen, S., Vikmoen, O., Slettaløkken, G. et al. Irisin and FNDC5: effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women. Eur J Appl Physiol 114, 1875–1888 (2014). https://doi.org/10.1007/s00421-014-2922-x

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