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Muscles and their myokines
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Summary: In the past, the role of physical activity as a life-style modulating factor has been considered as that of a tool to balance energy intake. Although it is important to avoid obesity, physical inactivity should be discussed in a much broader context. There is accumulating epidemiological evidence that a physically active life plays an independent role in the protection against type 2 diabetes, cardiovascular diseases, cancer, dementia and even depression. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an ‘exercise factor’, which could be released from skeletal muscle during contraction and mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We have suggested that cytokines or other peptides that are produced, expressed and released by muscle fibres and exert autocrine, paracrine or endocrine effects should be classified as ‘myokines’. Given that skeletal muscle is the largest organ in the human body, our discovery that contracting skeletal muscle secretes proteins sets a novel paradigm: skeletal muscle is an endocrine organ producing and releasing myokines, which work in a hormone-like fashion, exerting specific endocrine effects on other organs. Other myokines work via paracrine mechanisms, exerting local effects on signalling pathways involved in muscle metabolism. It has been suggested that myokines may contribute to exercise-induced protection against several chronic diseases.
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“Skeletal muscle contraction during RT triggers the production and release of cytokines such as interleukin (IL) and irisin, which exert effects both locally and in a crosstalk manner with other organs, such as the liver and adipose tissue, to cope with muscle repair, hypertrophy and fuel metabolism [6].”
From β-hydroxy-β -methylbutyrate supplementation benefits the effects of resistance training on body fat reduction via increased irisin expression in white adipose tissue (2021) · cites this paper as [6]
Experimental — accuracy not yet measuredIn the citing paper
“Several risk factors for MS are associated with physical inactivity, including low-grade inflammation and impaired metabolism (403, 404).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [403]
In the citing paper
“Several risk factors for MS are associated with physical inactivity, including low-grade inflammation and impaired metabolism (403, 404).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [404]
In the citing paper
“Conversely, prevention of physical inactivity through physical activity improves inflammatory markers by reducing resting CRP, interleukin-6 (IL-6), and tumour necrosis factor-α concentration (403).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [403]
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2 retracted
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Self-citationPredicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people
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CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK
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“THE JOURNAL OF EXPERIMENTAL BIOLOGY 342 increased bone mineral content, without appreciably affecting lean body mass or levels of other cytokines (Quinn et al., 2009).”
BackgroundNielsen, A. R., Mounier, R., Plomgaard, P., Mortensen, O. H., Penkowa, M., Speerschneider, T., Pilegaard, H., & Pedersen, B. K. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.139618 · Cited by 266
Self-citationPhysical Activity and Incident Cognitive Impairment in Elderly Persons
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“Sick Fat,” Metabolic Disease, and Atherosclerosis
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Self-citationEdward F. Adolph Distinguished Lecture: Muscle as an endocrine organ: IL-6 and other myokines
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Self-citationVoluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain
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Glucose Ingestion Attenuates Interleukin‐6 Release from Contracting Skeletal Muscle in Humans
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Self-citationFibroblast Growth Factor-21 Is Induced in Human Skeletal Muscles by Hyperinsulinemia
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Self-citationInterleukin‐6 release from the human brain during prolonged exercise
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Self-citationAssociation between Interleukin-15 and Obesity: Interleukin-15 as a Potential Regulator of Fat Mass
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Self-citationIL-6 signalling in exercise and disease
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Self-citationAbdominal Adiposity and Cardiometabolic Risk: Do We Have All the Answers?
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Interleukin-6 does/does not have a beneficial role in insulin sensitivity and glucose homeostasis
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Self-citationAdipokines, Myokines and Cardiovascular Disease
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Inflammation, Obesity, and the Metabolic Syndrome
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Human IL6 enhances leptin action in mice
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Self-citationPhysical Activity at Midlife in Relation to Successful Survival in Women at Age 70 Years or Older
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Fiber type specific expression of TNF-alpha, IL-6 and IL-18 in human skeletal muscles.
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Self-citationIs the anti-inflammatory effect of regular exercise responsible for reduced cardiovascular disease?
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Self-citationRole of interleukin‐6 signalling in glucose and lipid metabolism
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Self-citationVariability in Response to Antihypertensive Drugs
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BackgroundInfluence of AMP-activated protein kinase and calcineurin on metabolic networks in skeletal muscle
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3 of the 155 references couldn’t be matched to a known paper.
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Self-citationSkeletal muscle: A review of molecular structure and function, in health and disease
Mukund, K., & Subramaniam, S. (2019) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1462 · Cited by 789
McArdle, M. A., Finucane, O. M., Connaughton, R. M., McMorrow, A. M., & Roche, H. M. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00052 · Cited by 552
Metadata
- Authors
- Pedersen, B. K.
- Affiliations
- Rigshospitalet (DK)
- Corresponding author
- Pedersen, Bente Klarlund
- Venue
- Journal of Experimental Biology
- Publisher
- The Company of Biologists
- Published
- 2011-01-15
- Volume
- 214
- Issue
- 2
- Pages
- 337-346
- ISSN
- 0022-0949 (ISSN-L)
- 1477-9145
- OpenAlex
- W2033127864
- Cited by
- 668
- References
- 155
- Citations by year
- 2026: 19 · 2025: 26 · 2024: 55 · 2023: 34 · 2022: 46 · 2021: 58 · 2020: 59 · 2019: 39 · 2018: 49 · 2017: 50 · 2016: 46 · 2015: 45 · 2014: 43 · 2013: 46 · 2012: 41
- FWCI
- 32.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Experimental Biology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Funders
- Strategiske Forskningsråd (09-067009 and 09-075724, 09–067009, 09 – 075724)
- Sundhed og Sygdom, Det Frie Forskningsråd
- National Research Foundation
- Danmarks Grundforskningsfond (# 02-512-55, 09-067009, 09-075724)
- Ministério da Ciência, Tecnologia e Inovação
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- 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
- myokines, skeletal muscle, physical activity, paracrine signaling, autocrine signaling, exercise-induced metabolic changes, type 2 diabetes, cardiovascular disease, cancer, dementia, depression, physical inactivity, obesity
- MeSH terms
- Adipose Tissue, Animals, Cardiovascular Diseases, Chronic Disease, Diabetes Mellitus, Type 2, Humans, Motor Activity, Neoplasms, Exercise, Interleukin-6, Cytokines, Muscle, Skeletal, Neurodegenerative Diseases
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