The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Exercise-Induced Irisin Secretion Is Independent of Age or Fitness Level and Increased Irisin May Directly Modulate Muscle Metabolism Through AMPK Activation
Abstract
CONTEXT: Irisin has been proposed to be a myokine mediating the effect of exercise on adipocyte browning. The physiology of irisin in humans is not completely understood. OBJECTIVE: To study the physiology of irisin in healthy individuals with different age and fitness levels and to explore the direct effects of irisin on muscle metabolism. DESIGN, SETTING, AND SUBJECTS: Treadmill exercise studies were conducted to measure circulating irisin at baseline and in response to exercise among old and young, physically active and sedentary individuals. Also, high- and moderate-intensity swimming was performed in adolescent men and women to study the effect of exercise intensity and the time course of irisin induction by acute bouts of exercise. Human myotubes were treated with recombinant irisin, and the effect on gene expression, cell signaling, and metabolism was examined. RESULTS: Baseline circulating irisin was lower in old (vs young) and physically active (vs sedentary) subjects. Despite differences in basal levels, the percentage increase of irisin by acute bouts of exercise was not related to age or fitness level. The time course study revealed that circulating irisin increased immediately after high-intensity interval exercise and declined 1 hour thereafter. In vitro experiments showed that irisin facilitates glucose and lipid metabolism in human muscle through AMP kinase phosphorylation. CONCLUSIONS: Despite the differences in basal irisin levels, exercise-induced irisin secretion is independent of age or fitness level. Increased irisin can directly modulate muscle metabolism through AMP kinase activation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Increased irisin can directly modulate muscle metabolism through 5' AMP-activated protein kinase (AMPK) activation (Huh et al., 2014).”
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 Huh et al., 2014
In the citing paper
“(1) higher irisin serum levels in the younger group compared to the older group (age effect)”
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 Huh et al., 2014
In the citing paper
“Exercise-inducible myokines, such as irisin [62,63], IL-6 [76,77], IL-15 [91,126], BAIBA [111], and METRNL [100], as well as the osteokine OCN [71] have been shown to directly stimulate oxidative metabolism in autocrine and endocrine ways, respectively (1).”
In the citing paper
“(2) serum irisin levels were elevated in the swimmer groups (training effect)”
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 Huh et al., 2014
In the citing paper
“despite the differences in basal irisin levels, exercise-induced irisin secretion is independent of age or fitness level.”
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 Huh et al., 2014
In the citing paper
“(4) Higher rates of irisin were related to the metabolism of glucose and lipids in SkM through AMPK phosphorylation”
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 Huh et al., 2014
In the citing paper
“(3) rates of plasma irisin were related to the intensity of exercise training, with the group that performed intermittent high-intensity exercise having higher levels”
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 Huh et al., 2014
In the citing paper
“In this respect, irisin secretion was observed in volunteers of different ages submitted to a protocol of aerobic exercise of moderate to maximum intensity (70–75% VO2max until exhaustion; Huh et al., 2014).”
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 Huh et al., 2014
In the citing paper
“In this study, it was possible to verify that intense exercise, until exhaustion, promoted higher irisin serum levels after exercise in the young group compared to the old group (age 67.9 ± 5.0).”
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 Huh et al., 2014
In the citing paper
“It was observed that there was a significant increase in serum irisin levels immediately and up to 1 h after an exercise session in the group that practiced high-intensity swimming compared to the moderate intensity group.”
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 Huh et al., 2014
Citations
Cites
(2014) · Medical Entomology and Zoology · Cited by 9,400
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
Identification and Importance of Brown Adipose Tissue in Adult Humans
Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810780 · Cited by 4,399
Cold-Activated Brown Adipose Tissue in Healthy Men
van Marken Lichtenbelt, W. D., Vanhommerig, J. W., Smulders, N. M., Drossaerts, J. M. A. F. L., Kemerink, G. J., Bouvy, N. D., Schrauwen, P., & Teule, G. J. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808718 · Cited by 3,452
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
Brown and beige fat: Development, function and therapeutic potential
Harms, M., & Seale, P. (2013) · Nature Medicine · doi:10.1038/nm.3361 · Cited by 2,328
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
Guidelines for Exercise Testing and Prescription
Sharp, N. C. C. (1993) · British Journal of Sports Medicine · doi:10.1136/bjsm.27.2.138-a · Cited by 1,190
Adipose tissue browning and metabolic health
Bartelt, A., & Heeren, J. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.204 · Cited by 1,177
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
Self-citationPhysical Activity/Exercise and Type 2 Diabetes
Sigal, R. J., Kenny, G. P., Wasserman, D. H., Castaneda-Sceppa, C., & White, R. D. (2006) · Diabetes Care · doi:10.2337/dc06-9910 · Cited by 949
Guidelines for Exercise Testing and Prescription
Scavarda, A. (1986) · Military Medicine · doi:10.1093/milmed/151.9.465a · Cited by 842
Interleukin-6 in acute exercise and training: what is the biological relevance?
Fischer, C. P. (2026) · PubMed · doi:10.22029/eir.2006.1620 · Cited by 817
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 · cited 1×
“There are reports suggesting white adipose tissue as a source of irisin secretion (16, 34), but the exercise-induced burst in irisin is likely accounted for skeletal muscle release alone.”
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
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
Self-citationKurdiova, T., Balaz, M., Vician, M., Maderova, D., Vlcek, M., Valkovic, L., Srbecky, M., Imrich, R., Kyselovicova, O., Belan, V., et al. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.264655 · Cited by 401
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
Evidence against a Beneficial Effect of Irisin in Humans
Raschke, S., Elsen, M., Gassenhuber, J., Sommerfeld, M. R., Schwahn, U., Brockmann, B., Jung, R., Wisløff, U., Tjønna, A. E., Raastad, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073680 · Cited by 327
Lebrun, C. M. (2011) · Yearbook of Sports Medicine · doi:10.1016/j.yspm.2011.03.038 · Cited by 325
BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis
Qian, S., Tang, Y., Li, X., Liu, Y., Zhang, Y.-Y., Huang, H.-Y., Xue, R.-D., Yu, H.-Y., Guo, L., Gao, H.-D., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215236110 · Cited by 320
Huh, J. Y., Dincer, F., Mesfum, E., & Mantzoros, C. S. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.42 · Cited by 309
Pekkala, S., Wiklund, P. K., Hulmi, J. J., Ahtiainen, J. P., Horttanainen, M., Pöllänen, E., Mäkelä, K. A., Kainulainen, H., Häkkinen, K., Nyman, K., et al. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.263707 · Cited by 292 · cited 1×
“In this respect, some studies have failed to detect a rise in irisin levels due to delayed sampling time (16, 18).”
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
Effects of resistance training on the inflammatory response
Calle, M. C., & Fernández, M. L. (2010) · Nutrition Research and Practice · doi:10.4162/nrp.2010.4.4.259 · Cited by 247
Kraemer, R. R., Shockett, P. E., Webb, N., Shah, U. R., & Castracane, V. D. (2013) · Hormone and Metabolic Research · doi:10.1055/s-0033-1355381 · Cited by 181
Characterization of the metabolic effects of irisin on skeletal muscle in vitro
Vaughan, R. A., Gannon, N. P., Barberena, M. A., Garcia‐Smith, R., Bisoffi, M., Mermier, C. M., Conn, C. A., & Trujillo, K. A. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12268 · Cited by 150
Training and overtraining: an overview and experimental results in endurance sports.
Lehmann, M. J., Lormes, W., Opitz-Gress, A., Steinacker, J. M., Netzer, N. C., Foster, C., & Gastmann, U. (1997) · PubMed · Cited by 148
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
Self-citationIrisin in response to acute and chronic whole-body vibration exercise in humans
Huh, J. Y., Mougios, V., Skraparlis, A. N., Kabasakalis, A., & Mantzoros, C. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.04.001 · Cited by 115
Self-citationBori, Z., Zhao, Z., Koltai, E., Fatouros, I. G., Jamurtas, A. Z., Douroudos, I. I., Terzis, G., Chatzinikolaou, A., Sovatzidis, A., Draganidis, D., et al. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.03.004 · Cited by 108
Self-citationIrisin 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
Self-citationVamvini, M. T., Aronis, K. N., Panagiotou, G., Huh, J. Y., Chamberland, J. P., Brinkoetter, M. T., Petrou, M., Christophi, C. A., Kales, S. N., Christiani, D. C., et al. (2013) · European Journal of Endocrinology · doi:10.1530/eje-13-0276 · Cited by 65
Self-citationKraemer, R. R., Shockett, P. E., Webb, N. D., Shah, U. R., & Castracane, V. D. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000494385.02684.8b · Cited by 56
Irisin, the metabolic syndrome and follistatin in humans
Boström, P., & Fernández‐Real, J. M. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.230 · Cited by 37
Saraslanidis, P., Petridou, A., Bogdanis, G. C., Galanis, N., Tsalis, G. A., Kellis, S., & Mougios, V. (2011) · Journal of Sports Sciences · doi:10.1080/02640414.2011.583672 · Cited by 29
Self-citationEvidence against a beneficial effect of irisin in humans
Raschke, S., Elsen, M., Romacho, T., Eckardt, K., & Eckel, J. (2013) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0033-1336630 · Cited by 13
Flagged first, then by citations
Cited by
Sorted by citations
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
Self-citationDetection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry
Jedrychowski, M. P., Wrann, C. D., Paulo, J. A., Gerber, K. K., Szpyt, J., Robinson, M. M., Nair, K. S., Gygi, S. P., & Spiegelman, B. M. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.08.001 · Cited by 585
AMPK in skeletal muscle function and metabolism
Kjøbsted, R., Hingst, J. R., Fentz, J., Foretz, M., Sanz, M.-N., Pehmøller, C. K., Shum, M., Marette, A., Mounier, R., Treebak, J. T., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201700442r · Cited by 517
PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation
Cheng, C., Ku, H., & Lin, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113447 · Cited by 450
Leal, L. G., Lopes, M. A., & Batista, M. L. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01307 · Cited by 382
“Increased irisin can directly modulate muscle metabolism through 5’ AMP-activated protein kinase (AMPK) activation (Huh et al., 2014).”
Background
Metadata
- Authors
- Huh, J. Y., Mougios, V., Kabasakalis, A., Fatouros, I., Siopi, A., Douroudos, I. I., Filippaios, A., Panagiotou, G., Park, K. H., & Mantzoros, C. S.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Aristotle University of Thessaloniki (GR)
- Democritus University of Thrace (GR)
- Corresponding author
- Mantzoros, Christos S.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-11
- Volume
- 99
- Issue
- 11
- Pages
- E2154-E2161
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2129245678
- Cited by
- 363
- References
- 38
- Citations by year
- 2026: 24 · 2025: 25 · 2024: 39 · 2023: 25 · 2022: 49 · 2021: 35 · 2020: 29 · 2019: 22 · 2018: 39 · 2017: 33 · 2016: 14 · 2015: 26 · 2014: 2
- FWCI
- 16.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Office of Research and Development
- Clinical Science Research and Development
- 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
- irisin, physical activity, myokines, AMPK, muscle metabolism, aging, physical fitness, exercise intensity, high-intensity interval training, glucose metabolism, lipid metabolism, myotubes, adipocyte browning
- MeSH terms
- Adenylate Kinase, Adolescent, Adult, Age Factors, Aged, Female, Fibronectins, Humans, Male, Middle Aged, Physical Fitness, Signal Transduction, Exercise, Muscle, Skeletal, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
