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Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans
Abstract
Background Irisin is a recently identified exercise-induced myokine suggested to induce browning of white adipocytes. Deficiency of myostatin, and thus stimulation of muscle growth, has also been reported to induce irisin and its precursor FNDC5 expression in muscle and drive the browning of white adipocytes in mice, implying that irisin may be related to muscle growth in addition to its beneficial effects in adipocytes. In humans, the effect of irisin in muscle hypertrophy as well as adipocyte metabolism has not been fully investigated.Methods Primary cultured human myocytes/adipocytes and 3T3-L1 cells were used to examine irisin-regulated gene/protein expression. Lipid accumulation, ATP content, glycolysis, lipolysis and metabolite profile were measured in control and irisin-treated (10 and 50 nM) adipocytes.Results In human myocytes, FNDC5 mRNA and irisin secretion were increased during myogenic differentiation, along with PGC1α and myogenin expression. Irisin treatment significantly increased insulin-like growth factor 1 and decreased myostatin gene expression through ERK pathway. PGC1α4, a newly discovered PGC1α isoform specifically related to muscle hypertrophy, was also upregulated. In human adipocytes, irisin induced uncoupling protein 1 and consequently increased adipocyte energy expenditure, expression of metabolic enzymes and metabolite intermediates, resulting in inhibition of lipid accumulation. Irisin and FNDC5 treatment also reduced preadipocyte differentiation, suggesting an additional mechanism in suppressing fat mass.Conclusions These results suggest that irisin/FNDC5 has a pleiotropic role in muscle and improvement of adipocyte metabolism in humans.
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“The possibility of an inter-myokine axis with irisin [44,49] and crosstalk with follistatin could represent a mechanism through which myostatin is decreased by exercise.”
In the citing paper
“Likewise, exercise-induced reduction of myostatin by irisin [44] (7a) was described to reduce availability of myostatin to engage in proinflammatory responses [116] (7b).”
In the citing paper
“while irisin exerts a dual effect by also inhibiting myostatin [44] (2b)”
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Cites
Tuomilehto, J., Lindström, J., Eriksson, J. G., Valle, T. T., Hämäläinen, H., Ilanne-Parikka, P., Keinänen-Kiukaanniemi, S., Laakso, M., Louheranta, A., Rastas, M., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200105033441801 · Cited by 10,873
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., Rasbach, K. A., Boström, E. A., Choi, J. H., Long, J. Z., et al. (2012) · Nature · doi:10.1038/nature10777 · Cited by 4,810
Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909
MetaboAnalyst: a web server for metabolomic data analysis and interpretation
Xia, J., Psychogios, N., Young, N., & Wishart, D. S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp356 · Cited by 2,238
Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation
Egan, B., & Zierath, J. R. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.012 · Cited by 2,084
Colberg, S. R., Sigal, R. J., Fernhall, B., Regensteiner, J. G., Blissmer, B. J., Rubin, R. R., Chasan-Taber, L., Albright, A. L., & Braun, B. (2010) · Diabetes Care · doi:10.2337/dc10-9990 · Cited by 1,955
Mechanisms regulating skeletal muscle growth and atrophy
Schiaffino, S., Dyar, K. A., Ciciliot, S., Blaauw, B., & Sandri, M. (2013) · The FEBS Journal · doi:10.1111/febs.12253 · Cited by 1,492
Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway
Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., Lin, J. D., Greenberg, M. E., & Spiegelman, B. M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.008 · Cited by 1,440
Yuan, M., Breitkopf, S. B., Yang, X., & Asara, J. M. (2012) · Nature Protocols · doi:10.1038/nprot.2012.024 · Cited by 1,122
Nocon, M., Hiemann, T., Müller-Riemenschneider, F., Thalau, F., Roll, S., & Willich, S. N. (2008) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1097/hjr.0b013e3282f55e09 · Cited by 1,080
A global test for groups of genes: testing association with a clinical outcome
Goeman, J. J., van de Geer, S., de Kort, F., & van Houwelingen, H. C. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg382 · Cited by 1,052
Huh, J. Y., Panagiotou, G., Mougios, V., Brinkoetter, M., Vamvini, M. T., Schneider, B. E., & Mantzoros, C. S. (2012) · Metabolism · doi:10.1016/j.metabol.2012.09.002 · Cited by 1,040
Moreno-Navarrete, J. M., Ortega, F., Serrano, M., Guerra, E., Pardo, G., Tinahones, F., Ricart, W., & Fernández-Real, J. M. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2749 · Cited by 788
Zhang, Y., Li, R., Meng, Y., Li, S., Donelan, W., Zhao, Y., Qi, L., Zhang, M., Wang, X., Cui, T., et al. (2014) · Diabetes · doi:10.2337/db13-1106 · Cited by 733
A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy
Ruas, J. L., White, J. P., Rao, R. R., Kleiner, S., Brannan, K. T., Harrison, B. C., Greene, N. P., Wu, J., Estall, J. L., Irving, B. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.050 · Cited by 677
FNDC5/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
Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome
Park, K., Zaichenko, L., Brinkoetter, M. T., Thakkar, B., Sahin-Efe, A., Joung, K. E., Tsoukas, M. A., Geladari, E. V., Huh, J. Y., Dincer, F., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2373 · Cited by 513
Shan, T., Liang, X., Bi, P., & Kuang, S. (2013) · The FASEB Journal · doi:10.1096/fj.12-225755 · Cited by 301
Adipo-myokines: two sides of the same coin–mediators of inflammation and mediators of exercise
Raschke, S., & Eckel, J. (2013) · Mediators of Inflammation · doi:10.1155/2013/320724 · Cited by 296
Pharmacological and nutritional agents promoting browning of white adipose tissue
Bonet, M. L., Oliver, P., & Palou, A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.12.002 · Cited by 286
Irisin and exercise training in humans – Results from a randomized controlled training trial
Hecksteden, A., Wegmann, M., Steffen, A., Kraushaar, J., Morsch, A., Ruppenthal, S., Kaestner, L., & Meyer, T. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-235 · Cited by 254
Irisin-immunoreactivity in neural and non-neural cells of the rodent
Dun, S. L., Lyu, R., Chen, Y., Chang, J. K., Luo, J. J., & Dun, N. J. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.02.050 · Cited by 240
Raschke, S., Eckardt, K., Bjørklund Holven, K., Jensen, J., & Eckel, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062008 · Cited by 199
Aydın, S., Kuloğlu, T., Aydin, S., Eren, M. N., Çelik, A., Yılmaz, M., Kalaycı, M. Z., Şahin, İ., Gungor, O., Gürel, A., et al. (2013) · Peptides · doi:10.1016/j.peptides.2013.11.024 · Cited by 168
Huh, J. Y., Kim, Y., Jeong, J., Park, J., Kim, I., Huh, K. H., Kim, Y. S., Woo, H. A., Rhee, S. G., Lee, K., et al. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3766 · Cited by 158
Gouni‐Berthold, I., Berthold, H. K., Huh, J. Y., Berman, R., Spenrath, N., Krone, W., & Mantzoros, C. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072858 · Cited by 134
Kelly, D. P. (2012) · Science · doi:10.1126/science.1221688 · Cited by 133
Irisin: A renaissance in metabolism?
Polyzos, S. A., Kountouras, J., Shields, K., & Mantzoros, C. S. (2013) · Metabolism · doi:10.1016/j.metabol.2013.04.008 · Cited by 131
Transcriptional Regulation of Adipocyte Hormone-Sensitive Lipase by Glucose
Smih, F., Rouet, P., Lucas, S., Mairal, A., Sengenès, C., Lafontan, M., Vaulont, S., Casado, M., & Langin, D. (2002) · Diabetes · doi:10.2337/diabetes.51.2.293 · Cited by 83
Irisin in humans: recent advances and questions for future research
Boström, P., Fernández‐Real, J. M., & Mantzoros, C. S. (2013) · Metabolism · doi:10.1016/j.metabol.2013.11.009 · Cited by 79
Resistance Exercise Training does not Affect Plasma Irisin Levels of Hemodialysis Patients
Moraes, C., Leal, V. D. O., Marinho, S. M., Barroso, S. G., Rocha, G. D. S., Boaventura, G. T., & Mafra, D. (2013) · Hormone and Metabolic Research · doi:10.1055/s-0033-1354402 · Cited by 78
Exercise and type 2 diabetes: New prescription for an old problem
Bird, S. R., & Hawley, J. A. (2012) · Maturitas · doi:10.1016/j.maturitas.2012.05.015 · Cited by 66
Irisin—behind the benefits of exercise
Cunha, A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.11 · Cited by 23
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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
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Cheng, C., Ku, H., & Lin, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113447 · Cited by 450
Huh, J. Y., Mougios, V., Kabasakalis, A., Fatouros, I., Siopi, A., Douroudos, I. I., Filippaios, A., Panagiotou, G., Park, K. H., & Mantzoros, C. S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1437 · Cited by 363
Metadata
- Authors
- Huh, J. Y., Dincer, F., Mesfum, E., & Mantzoros, C. S.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Mantzoros, C S
- Venue
- International Journal of Obesity
- Published
- 2014-03-11
- Volume
- 38
- Issue
- 12
- Pages
- 1538-1544
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2022352721
- Cited by
- 309
- References
- 33
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 28 · 2023: 30 · 2022: 56 · 2021: 27 · 2020: 24 · 2019: 23 · 2018: 15 · 2017: 25 · 2016: 18 · 2015: 14 · 2014: 11
- FWCI
- 15.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- irisin, FNDC5, myokines, muscle hypertrophy, adipogenesis, adipocyte metabolism, white adipose tissue browning, myostatin, insulin-like growth factor I, ERK signaling, UCP1, energy expenditure, lipid accumulation, preadipocyte differentiation, 3T3-L1 adipocytes
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Fibronectins, Gene Expression Regulation, Humans, Insulin Resistance, RNA, Messenger, Blotting, Western, Biomarkers, Adipocytes, Muscle, Skeletal, Myocytes, Smooth Muscle, 3T3-L1 Cells, Mice
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