Muscles, exercise and obesity: skeletal muscle as a secretory organ

Abstract

During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.

Key Points

  • Myokines are cytokines or other peptides that are produced, expressed and released by muscle fibres

  • Myokines may exert autocrine, paracrine or endocrine effects

  • Myokines may balance and counteract the effects of adipokines

  • The muscle–cell secretome consists of several hundred secreted products

  • Identified myokines include myostatin, LIF, IL-6, IL-7, BDNF, IGF-1, FGF-2, FSTL-1 and irisin

  • Myokines may mediate protective effects of muscular exercise, with regard to diseases associated with a physically inactive lifestyle

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Figure 1: Interplay between adipokines and myokines represent a yin–yang balance.
Figure 2: Skeletal muscle is a secretory organ.
Figure 3: Links between physical inactivity and disease development.
Figure 4

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Acknowledgements

B. K. Pedersen is supported by a grant from the Danish National Research Foundation (#02-512-55). M. A. Febbraio is supported by grants from the National Health and Medical Research Council (NHMRC), The Diabetes Australia Research Trust and the Victorian Government Operational Infrastructure Support Program.

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Correspondence to Bente K. Pedersen.

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Pedersen, B., Febbraio, M. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8, 457–465 (2012). https://doi.org/10.1038/nrendo.2012.49

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