Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content
Abstract
In humans, the plasma interleukin 6 (IL‐6) concentration increases dramatically during low‐intensity exercise. Measurements across the working limb indicate that skeletal muscle is the source of IL‐6 production. To determine whether energy availability influences the regulation of IL‐6 expression during prolonged exercise, six male subjects completed two trials consisting of 180 min of two‐legged dynamic knee extensor with either normal or low (~60% of control) pre‐exercise muscle glycogen levels. Increases in plasma IL‐6 during exercise were significantly higher ( P < 0.05) in the low‐glycogen (16‐fold) trial verses the control (10‐fold) trial. Transcriptional activation of the IL‐6 gene in skeletal muscle was also higher in the low‐glycogen trial; it increased by about 40‐fold after 90 min of exercise and about 60‐fold after 180 min of exercise. Muscle IL‐6 mRNA followed a similar but delayed pattern, increasing by more than 100‐fold in the low‐glycogen trial and by about 30‐fold in the control trial. These data demonstrate that exercise activates transcription of the IL‐6 gene in working skeletal muscle, a response that is dramatically enhanced when glycogen levels are low. These findings also support the hypothesis that IL‐6 may be produced by contracting myofibers when glycogen levels become critically low as a means of signaling the liver to increase glucose production.
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High levels of IL-6 are observed when glycogen levels are low, as a response to metabolic demand.
“High levels of IL-6 are observed in situations where glycogen levels are low, as a response to metabolic demand”
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 Keller et al., 2001
Higher levels of IL-6 are related to a higher lipolytic rate by activation of the AMPK pathway and/or PI3-kinase, activating fatty acid oxidation and increasing energy supply.
“since higher levels of IL-6 are related to a higher lipolytic rate by activation of the AMPK pathway and/or PI3-kinase activating the oxidation of the fatty acids which leads to greater availability of energy supply from this energy source (Keller et al., 2001).”
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 Keller et al., 2001
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Self-citation
- Authors
- Keller, C., Steensberg, A., Pilegaard, H., Osada, T., Saltin, B., Pedersen, B. K., & Neufer, P. D.
- Affiliations
- University of Copenhagen (DK)
- Tokyo Medical University (JP)
- Copenhagen Muscle Research Centre (DK)
- Yale University (US)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2001-10-29
- Volume
- 15
- Issue
- 14
- Pages
- 1-15
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2088094751
- Cited by
- 514
- References
- 4
- Citations by year
- 2026: 15 · 2025: 10 · 2024: 13 · 2023: 16 · 2022: 20 · 2021: 19 · 2020: 22 · 2019: 18 · 2018: 17 · 2017: 25 · 2016: 18 · 2015: 30 · 2014: 25 · 2013: 36 · 2012: 24
- FWCI
- 26.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Danmarks Grundforskningsfond (504-14)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-45372)
- 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 › Cell Biology › Muscle metabolism and nutrition
- Keywords
- interleukin-6, skeletal muscle, muscle glycogen, physical activity, low-intensity exercise, muscle contraction, IL-6 mRNA, energy availability, glucose production, knee extension exercise
- MeSH terms
- Glycogen, Humans, Male, Muscle Contraction, RNA, Messenger, Time Factors, Transcription, Genetic, Exercise, Transcriptional Activation, Interleukin-6, Muscle, Skeletal, Reverse Transcriptase Polymerase Chain Reaction
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