Interleukin-6 release from human skeletal muscle during exercise: relation to AMPK activity
Abstract
We tested the hypothesis that IL-6 release from muscle during exercise may be related to muscle activity of 5'-AMP-activated protein kinase (AMPK). Eight healthy, well-trained young men completed two 60-min trials on a bicycle ergometer at 70% of their peak oxygen uptake in either a glycogen-depleted or a glycogen-loaded state. IL-6 was released from the leg already after 10 min of exercise in the glycogen-depleted state, whereas no significant release was observed at any time in the loaded state. Nevertheless, plasma IL-6 increased similarly in the two trials from approximately 0.8 pg/ml at rest to approximately 4.5 pg/ml after 60 min of exercise. Activity of alpha1-AMPK (160%) and alpha2-AMPK (145%) was increased at rest in the glycogen-depleted compared with the loaded situation. During exercise, alpha1-AMPK activity did not change from resting levels in both trials, whereas alpha2-AMPK activity increased only in the glycogen-depleted state. After 60 min of exercise in the glycogen-depleted state, individual values of alpha2-AMPK activity correlated significantly (r = 0.87, P < 0.006) with individual values of IL-6 release as well as with average IL-6 release over the entire 60 min (r = 0.86, P < 0.006). The present data are compatible with a role for AMPK in IL-6 release during exercise or a role for IL-6 in activating AMPK. Alternatively, both AMPK and IL-6 are independent sensors of a low muscle glycogen concentration during exercise. In addition, leg release of IL-6 cannot alone explain the increase in plasma IL-6 during exercise.
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The increase in circulating IL-6 after exercise does not appear linear over time; an exponential acceleration in IL-6 secretion occurs soon after exercise.
“However, the increase in circulating IL-6 after exercise does not appear linearly over time, with a study finding an exponential acceleration in IL-6 secretion soon after exercise (Macdonald et al., 2003).”
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 Macdonald et al., 2003
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- Authors
- MacDonald, C., Wojtaszewski, J. F. P., Pedersen, B. K., Kiens, B., & Richter, E. A.
- Affiliations
- University of Copenhagen (DK)
- ORCID
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2003-12
- Volume
- 95
- Issue
- 6
- Pages
- 2273-2277
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2053431552
- Cited by
- 105
- References
- 23
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 7 · 2012: 7
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- interleukin-6, skeletal muscle, AMPK, physical activity, muscle glycogen depletion, energy sensing, trained men
- MeSH terms
- Adult, Catecholamines, Diet, Glycogen, Humans, Leg, Male, Pulmonary Gas Exchange, Regional Blood Flow, Exercise, Interleukin-6, Cyclic AMP-Dependent Protein Kinases, Muscle, Skeletal
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