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.
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Increased irisin can directly modulate muscle metabolism through AMPK activation.
“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 healthy swimmers of different ages, higher irisin serum levels were found in the younger group compared to the older group (age effect).
“(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
Exercise-inducible myokines irisin, IL-6, IL-15, BAIBA, and METRNL, as well as osteokine OCN, directly stimulate oxidative metabolism in autocrine and endocrine ways.
“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 healthy swimmers, serum irisin levels were elevated in the swimmer groups (training effect).
“(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
Exercise-induced irisin secretion is independent of age or fitness level.
“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
Higher rates of irisin were related to the metabolism of glucose and lipids in skeletal muscle through AMPK phosphorylation.
“(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
Plasma irisin rates were related to the intensity of exercise training, with the group that performed intermittent high-intensity exercise having higher levels.
“(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 volunteers of different ages submitted to aerobic exercise of moderate to maximum intensity (70-75% VO2max until exhaustion), irisin secretion was observed.
“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
Intense exercise until exhaustion promoted higher irisin serum levels after exercise in the young group compared to the old group.
“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 swimming adolescents, there was a significant increase in serum irisin levels immediately and up to 1 h after an exercise session in the high-intensity swimming group compared to the moderate intensity group.
“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
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“Increased irisin can directly modulate muscle metabolism through 5’ AMP-activated protein kinase (AMPK) activation (Huh et al., 2014).”
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- 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 › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Epidemiology › 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
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