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Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health?
Open accessAbstract
Key points Contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis and metabolic health, and the associated regulatory role of exercise and PGC‐1α. We analysed the effects of different short‐ and long‐term exercise regimens on muscle FNDC5 and PGC‐1α, and serum irisin, and studied the associations of irisin and FNDC5 with health parameters. FNDC5 and serum irisin did not change after acute aerobic, long‐term endurance training or endurance training combined with resistance exercise (RE) training, or associate with metabolic disturbances. A single RE bout increased FNDC5 mRNA in young, but not older men (27 vs. 62 years). Changes in PGC‐1α or serum irisin were not consistently accompanied by changes in FNDC5. Our data suggest that the effects of exercise on FNDC5 and irisin are not consistent, and that their role in health is questionable. Moreover, the regulatory mechanisms should be studied further. Abstract Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC‐1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC‐1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low‐intensity aerobic exercise (AE) (middle‐aged, n= 17), (2) a heavy‐intensity resistance exercise (RE) bout (young n= 10, older n= 11) (27 vs. 62 years), (3) long‐term 21 weeks endurance exercise (EE) training alone (twice a week, middle‐aged, n= 9), or (4) combined EE and RE training (both twice a week, middle‐aged, n= 9). Skeletal muscle mRNA expression was analysed by quantitative PCR and serum irisin by ELISA. No significant changes were observed in skeletal muscle PGC‐1α, FNDC5 and serum irisin after AE, EE training or combined EE + RE training. However, a single RE bout increased PGC‐1α by 4‐fold in young and by 2‐fold in older men, while FNDC5 mRNA only increased in young men post‐RE, by 1.4‐fold. Changes in PGC‐1α or serum irisin were not consistently accompanied by changes in FNDC5. In conclusion, for the most part, neither longer‐term nor single exercise markedly increases skeletal muscle FNDC5 expression or serum irisin. Therefore their changes in response to exercise are probably random and not consistent excluding the confirmation of any definitive link between exercise and FNDC5 expression and irisin release in humans. Moreover, irisin and FNDC5 were not associated with glucose tolerance and being overweight, or with metabolic disturbances, respectively. Finally, factor(s) other than PGC‐1α and transcription may regulate FNDC5 expression.
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“In this study, it was observed that muscle irisin levels were only increased in the young group that performed a single resistance training session, without any changes in irisin serum levels regardless of training.”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Pekkala et al., 2013
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“No association was found between levels of FNDC5 and health parameters (Table 1).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Pekkala et al., 2013
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Citations
Cites
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
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“Yet, the latest reports showed that skeletal muscle FNDC5 expression and circulating irisin levels were decreased in obese patients and associated with insulin sensitivity, and that adipose tissue might secrete irisin in response to exercise (Moreno-Navarrete et al. 2013; Roca-Rivada et al. 2013).”
BackgroundFNDC5/irisin is not only a myokine but also an adipokine
Roca-Rivada, A., Castelao, C., Senin, L. L., Landrove, M. O., Baltar, J., Crujeiras, A. B., Seoane, L. M., Casanueva, F. F., & Pardo, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060563 · Cited by 612 · cited 2×
“Yet, the latest reports showed that skeletal muscle FNDC5 expression and circulating irisin levels were decreased in obese patients and associated with insulin sensitivity, and that adipose tissue might secrete irisin in response to exercise (Moreno-Navarrete et al. 2013; Roca-Rivada et al. 2013).”
BackgroundMetabolic adaptations through the PGC‐1α and SIRT1 pathways
Rodgers, J. T., Lerin, C., Gerhart-Hines, Z., & Puigserver, P. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.11.034 · Cited by 561
Is irisin a human exercise gene?
Timmons, J. A., Baar, K., Davidsen, P. K., & Atherton, P. J. (2012) · Nature · doi:10.1038/nature11364 · Cited by 393
Role of N-glycosylation in trafficking of apical membrane proteins in epithelia
Vagin, O., Kraut, J. A., & Sachs, G. M. (2008) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.90340.2008 · Cited by 198
Hulmi, J. J., Kovanen, V., Selänne, H., Kraemer, W. J., Häkkinen, K., & Mero, A. A. (2009) · Amino Acids · doi:10.1007/s00726-008-0150-6 · Cited by 189
Self-citationProtein N-Glycosylation, Protein Folding, and Protein Quality Control
Roth, J., Zuber, C., Park, S., Jang, I., Lee, Y., Gaplovská-Kyselá, K., Fourn, V. L., Santimaria, R., Guhl, B., & Cho, J. W. (2010) · Molecules and Cells · doi:10.1007/s10059-010-0159-z · Cited by 183
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Kim, H., Wrann, C. D., Jedrychowski, M., Vidoni, S., Kitase, Y., Nagano, K., Zhou, C., Chou, J., Parkman, V.-J. A., Novick, S. J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.025 · Cited by 638
Physiology and role of irisin in glucose homeostasis
Perakakis, N., Triantafyllou, G. A., Fernández-Real, J. M., Huh, J. Y., Park, K. H., Seufert, J., & Mantzoros, C. S. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.221 · Cited by 621
Norheim, F., Langleite, T. M., Hjorth, M., Holen, T., Kielland, A., Stadheim, H. K., Gulseth, H. L., Birkeland, K. I., Jensen, J., & Drevon, C. A. (2014) · The FEBS Journal · doi:10.1111/febs.12619 · Cited by 563
Metadata
- Authors
- Pekkala, S., Wiklund, P. K., Hulmi, J. J., Ahtiainen, J. P., Horttanainen, M., Pöllänen, E., Mäkelä, K. A., Kainulainen, H., Häkkinen, K., Nyman, K., Alén, M., Herzig, K., & Cheng, S.
- Affiliations
- University of Jyväskylä (FI)
- University of Oulu (FI)
- Central Finland Health Care District (FI)
- Oulu University Hospital (FI)
- Kuopio University Hospital (FI)
- Corresponding author
- Pekkala, Satu
- ORCID
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2013-10-04
- Volume
- 591
- Issue
- 21
- Pages
- 5393-5400
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC3936375
- OpenAlex
- W1932144823
- Cited by
- 292
- References
- 16
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 18 · 2023: 12 · 2022: 33 · 2021: 25 · 2020: 16 · 2019: 17 · 2018: 31 · 2017: 17 · 2016: 16 · 2015: 34 · 2014: 35 · 2013: 8
- FWCI
- 21.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Jyväskylä University Digital Archive (University of Jyväskylä) (submittedVersion)
- Funders
- Diabetestutkimussäätiö
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- FNDC5, irisin, PGC-1α, skeletal muscle gene expression, resistance training, endurance training, aerobic exercise, exercise training, energy homeostasis, metabolic health, aging, age differences, serum biomarkers, exercise response variability, metabolic disorders, diabetes mellitus, cardiovascular risk factors, oxidative stress, insulin sensitivity, adipokines
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adult, Age Factors, Aged, Fibronectins, Humans, Male, Middle Aged, Physical Endurance, RNA, Messenger, Transcription Factors, Transcription, Genetic, Case-Control Studies, Muscle, Skeletal, Resistance Training
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