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01-09-2014 | Original Article

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

Authors: S. Ellefsen, O. Vikmoen, G. Slettaløkken, J. E. Whist, H. Nygaard, I. Hollan, I. Rauk, G. Vegge, T. A. Strand, T. Raastad, B. R. Rønnestad

Published in: European Journal of Applied Physiology | Issue 9/2014

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.

Available only for authorised users

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).

Adams GR, Hather BM, Baldwin KM, Dudley GA (1993) Skeletal muscle myosin heavy chain composition and resistance training. J Appl Physiol 74(2):911–915PubMed

Adams CM, Suneja M, Dudley-Javoroski S, Shields RK (2011) Altered mRNA expression after long-term soleus electrical stimulation training in humans with paralysis. Muscle Nerve 43(1):65–75. doi:10.1002/mus.21831 PubMedCentralPubMedCrossRef

Blomstrand E, Ekblom B (1982) The needle biopsy technique for fibre type determination in human skeletal muscle—a methodological study. Acta Physiol Scand 116(4):437–442. doi:10.1111/j.1748-1716.1982.tb07163.x PubMedCrossRef

Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM (2012) A PGC1-[agr]-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481(7382):463–468. doi:10.1038/nature10777

Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach Kyle A, Boström EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Højlund K, Gygi SP, Spiegelman BM (2012) Bostrom et al. reply. Nature 488(7413):E10–E11. doi:10.1038/nature11365

Diez D, Grijota-Martinez C, Agretti P, De Marco G, Tonacchera M, Pinchera A, Morreale de Escobar G, Bernal J, Morte B (2008) Thyroid hormone action in the adult brain: gene expression profiling of the effects of single and multiple doses of triiodo-l-thyronine in the rat striatum. Endocrinology 149(8):3989–4000. doi:10.1210/en.2008-0350 PubMedCrossRef

Dytham C (2011) Choosing and using statistics: a biologist’s guide. Wiley Publishing, New Jersey

Ellefsen S, Stensløkken KO (2010) Gene-family profiling: a normalization-free real-time RT-PCR approach with increased physiological resolution. Physiol Genomics 42(1):1–4PubMedCrossRef

Ellefsen S, Stenslokken K-O, Sandvik GK, Kristensen TA, Nilsson GE (2008) Improved normalization of real time RT PCR data using an external RNA control. Anal Biochem 376(1):83–93. doi:10.1016/j.ab.2008.01.028 PubMedCrossRef

Ellefsen S, Bliksøen M, Rutkovskiy A, Johansen IB, Kaljusto M-L, Nilsson GE, Vaage JI, Stenslokken K-O (2012) Per-unit-living tissue normalization of real-time RT-PCR data in ischemic rat hearts. Physiol Genomics 44(12):651–656. doi:10.1152/physiolgenomics.00004.2012 PubMedCrossRef

Ellefsen S, Vikmoen O, Zacharoff E, Rauk I, Slettaløkken G, Strand TA, Whist JE, Hanestadhaugen M, Vegge G, Fagernes CE, Nygaard H, Hollan I, Rønnestad BR (2014) Reliable determination of training-induced alterations in muscle fibre composition in human skeletal muscle using qPCR. Scand J Med Sci Sports. doi:10.1111/sms.12185

Enerback S (2013) ADIPOSE TISSUE METABOLISM IN 2012 Adipose tissue plasticity and new therapeutic targets. Nat Rev Endocrinol 9(2):69–70. doi:10.1038/nrendo.2012.242 PubMedCrossRef

Erickson HP (2013) Irisin and FNDC5 in retrospect: an exercise hormone or a transmembrane receptor? Adipocyte 2(4):289–293PubMedCentralPubMedCrossRef

Gundersen K (2011) Excitation-transcription coupling in skeletal muscle: the molecular pathways of exercise. Biol Rev Camb Philos Soc 86(3):564–600. doi:10.1111/j.1469-185X.2010.00161.x PubMedCentralPubMedCrossRef

Hanssen KE, Kvamme NH, Nilsen TS, Rønnestad B, Ambjørnsen IK, Norheim F, Kadi F, Hallèn J, Drevon CA, Raastad T (2012) The effect of strength training volume on satellite cells, myogenic regulatory factors, and growth factors. Scand J Med Sci Sports. doi:10.1111/j.1600-0838.2012.01452.x PubMed

Hecksteden A, Wegmann M, Steffen A, Kraushaar J, Morsch A, Ruppenthal S, Kaestner L, Meyer T (2013) Irisin and exercise training in humans—results from a randomized controlled training trial. BMC Med 11(1):235PubMedCrossRef

Hopkins WG, Marshall SW, Batterham AM, Hanin J (2009) Progressive statistics for studies in sports medicine and exercise science. Med Sci Sports Exerc 41(1):3–13PubMedCrossRef

Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, Mantzoros CS (2012) FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism 61(12):1725–1738. doi:10.1016/j.metabol.2012.09.002 PubMedCentralPubMedCrossRef

Irrcher I, Adhihetty PJ, Sheehan T, Joseph A-M, Hood DA (2003) PPARγ coactivator-1α expression during thyroid hormone- and contractile activity-induced mitochondrial adaptations. Am J Physiol Cell Physiol 284(6):C1669–C1677. doi:10.1152/ajpcell.00409.2002 PubMedCrossRef

Kadi F, Bonnerud P, Eriksson A, Thornell LE (2000) The expression of androgen receptors in human neck and limb muscles: effects of training and self-administration of androgenic-anabolic steroids. Histochem Cell Biol 113(1):25–29PubMedCrossRef

Kim B (2008) Thyroid hormone as a determinant of energy expenditure and the basal metabolic rate. Thyroid 18(2):141–144. doi:10.1089/thy.2007.0266 PubMedCrossRef

Kraemer RR, Shockett P, Webb ND, Shah U, Castracane VD (2013) A transient elevated irisin blood concentration in response to prolonged, moderate aerobic exercise in young men and women. Horm Metab Res (EFirst). doi:10.1055/s-0033-1355381

Krämer DK, Ahlsén M, Norrbom J, Jansson E, Hjeltnes N, Gustafsson T, Krook A (2006) Human skeletal muscle fibre type variations correlate with PPARα, PPARδ and PGC-1α mRNA. Acta Physiol (Oxf) 188(3–4):207–216. doi:10.1111/j.1748-1716.2006.01620.x CrossRef

Lee P, Linderman Joyce D, Smith S, Brychta Robert J, Wang J, Idelson C, Perron Rachel M, Werner Charlotte D, Phan Giao Q, Kammula Udai S, Kebebew E, Pacak K, Chen Kong Y, Celi Francesco S (2014) Irisin and FGF21 Are cold-induced endocrine activators of brown fat function in humans. Cell Metab 19(2):302–309. doi:10.1016/j.cmet.2013.12.017 PubMedCrossRef

Lin J, Wu H, Tarr PT, Zhang CY, Wu ZD, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418(6899):797–801. doi:10.1038/nature00904 PubMedCrossRef

Moreno-Navarrete JM, Ortega F, Serrano M, Guerra E, Pardo G, Tinahones F, Ricart W, Fernández-Real JM (2013) Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab 98(4):E769–E778. doi:10.1210/jc.2012-2749 PubMedCrossRef

Nebreda AR, Porras A (2000) p38 MAP kinases: beyond the stress response. Trends Biochem Sci 25(6):257–260. doi:10.1016/S0968-0004(00)01595-4 PubMedCrossRef

Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, Gulseth HL, Birkeland KI, Jensen J, Drevon CA (2014) The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS J 281(3):739–749. doi:10.1111/febs.12619 PubMedCrossRef

Norrbom J, Sundberg CJ, Ameln H, Kraus WE, Jansson E, Gustafsson T (2004) PGC-1α mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle. J Appl Physiol 96(1):189–194. doi:10.1152/japplphysiol.00765.2003 PubMedCrossRef

Novelle MG, Contreras C, Romero-Picó A, López M, Diéguez C (2013) Irisin, two years later. Int J Endocrinol 2013:8. doi:10.1155/2013/746281

Pekkala S, Wiklund PK, Hulmi JJ, Ahtiainen JP, Horttanainen M, Pöllänen E, Mäkelä KA, Kainulainen H, Häkkinen K, Nyman K, Alén M, Herzig K-H, Cheng S (2013) Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? J Physiol. doi:10.1113/jphysiol.2013.263707 PubMed

Plomgaard P, Penkowa M, Leick L, Pedersen BK, Saltin B, Pilegaard H (2006) The mRNA expression profile of metabolic genes relative to MHC isoform pattern in human skeletal muscles. J Appl Physiol 101(3):817–825. doi:10.1152/japplphysiol.00183.2006 PubMedCrossRef

Ramakers C, Ruijter JM, Deprez RH, Moorman AF (2003) Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett 339(1):62–66PubMedCrossRef

Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U, Brockmann B, Jung R, Wisløff U, Tjønna AE, Raastad T, Hallén J, Norheim F, Drevon CA, Romacho T, Eckardt K, Eckel J (2013) Evidence against a beneficial effect of irisin in humans. PLoS One 8(9):e73680. doi:10.1371/journal.pone.0073680 PubMedCentralPubMedCrossRef

Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, Crujeiras AB, Seoane LM, Casanueva FF, Pardo M (2013) FNDC5/irisin is not only a myokine but also an adipokine. PLoS One 8(4):e60563. doi:10.1371/journal.pone.0060563 PubMedCentralPubMedCrossRef

Rønnestad BR, Egeland W, Kvamme NH, Refsnes PE, Kadi F, Raastad T (2007) Dissimilar effects of one- and three-set strength training on strength and muscle mass gains in upper and lower body in untrained subjects. J Strength Cond Res 21(1):157–163PubMedCrossRef

Rønnestad B, Nygaard H, Raastad T (2011) Physiological elevation of endogenous hormones results in superior strength training adaptation. Eur J Appl Physiol 111(9):2249–2259. doi:10.1007/s00421-011-1860-0 PubMedCrossRef

Ruas Jorge L, White James P, Rao Rajesh R, Kleiner S, Brannan Kevin T, Harrison Brooke C, Greene Nicholas P, Wu J, Estall Jennifer L, Irving Brian A, Lanza Ian R, Rasbach Kyle A, Okutsu M, Nair KS, Yan Z, Leinwand Leslie A, Spiegelman Bruce M (2012) A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 151(6):1319–1331. doi:10.1016/j.cell.2012.10.050 PubMedCentralPubMedCrossRef

Ruijter JM, Ramakers C, Hoogaars WMH, Karlen Y, Bakker O, van den Hoff MJB, Moorman AFM (2009) Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res 37(6):12. doi:10.1093/nar/gkp045 CrossRef

Staron RS, Karapondo DL, Kraemer WJ, Fry AC, Gordon SE, Falkel JE, Hagerman FC, Hikida RS (1994) Skeletal muscle adaptations during early phase of heavy-resistance training in men and women. J Appl Physiol 76(3):1247–1255PubMed

Stengel A, Hofmann T, Goebel-Stengel M, Elbelt U, Kobelt P, Klapp BF (2013) Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity—correlation with body mass index. Peptides 39:125–130. doi:10.1016/j.peptides.2012.11.014 PubMedCrossRef

Timmons JA, Baar K, Davidsen PK, Atherton PJ (2012) Is irisin a human exercise gene? Nature 488(7413):E9–E10. doi:10.1038/nature11364 PubMedCrossRef

Tipton KD, Rasmussen BB, Miller SL, Wolf SE, Owens-Stovall SK, Petrini BE, Wolfe RR (2001) Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. Am J Physiol Endocrinol Metab 281(2):E197–E206PubMed

Tjørve E, Tjørve KMC, Olsen JO, Senum R, Oftebro H (2007) On commonness and rarity of thyroid hormone resistance: a discussion based on mechanisms of reduced sensitivity in peripheral tissues. Med Hypotheses 69(4):913–921. doi:10.1016/j.mehy.2006.12.056 PubMedCrossRef

Untergasser A, Nijveen H, Rao X, Bisseling T, Geurts R, Leunissen JAM (2007) Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Res 35(suppl 2):W71–W74. doi:10.1093/nar/gkm306 PubMedCentralPubMedCrossRef

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):RESEARCH0034PubMedCentralPubMedCrossRef

Vaughan RA, Gannon NP, Barberena MA, Garcia-Smith R, Bisoffi M, Mermier CM, Conn CA, Trujillo KA (2014) Characterization of the metabolic effects of irisin on skeletal muscle in vitro. Diabetes Obes Metab. doi:10.1111/dom.12268 PubMed

Vegge G, Ronnestad B, Ellefsen S (2012) Improved cycling performance with ingestion of hydrolyzed marine protein depends on performance level. J Int Soc Sports Nutr 9(1):14PubMedCentralPubMedCrossRef

Wrann Christiane D, White James P, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin Jiandie D, Greenberg Michael E, Spiegelman Bruce M (2013) Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab 18(5):649–659. doi:10.1016/j.cmet.2013.09.008 PubMedCrossRef

Title: Irisin and FNDC5: effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women
Authors: S. Ellefsen
O. Vikmoen
G. Slettaløkken
J. E. Whist
H. Nygaard
I. Hollan
I. Rauk
G. Vegge
T. A. Strand
T. Raastad
B. R. Rønnestad
Publication date: 01-09-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Applied Physiology / Issue 9/2014
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-014-2922-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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