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Cited by 58Adipokines, Inflammation, and Metabolic DiseasesExercise and Physiological ResponsesMuscle Physiology and Disorders

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Myokines: metabolic regulation in obesity and type 2 diabetes

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Chen, Zhi-Tian, Weng, Zhi-Xuan, Lin, Jiandie D, Meng, Zhuo-Xian·2024·Life Metabolism
DOI 10.1093/lifemeta/loae006PMC PMC11749576
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Abstract

Skeletal muscle plays a vital role in the regulation of systemic metabolism, partly through its secretion of endocrine factors which are collectively known as myokines. Altered myokine levels are associated with metabolic diseases, such as type 2 diabetes (T2D). The significance of interorgan crosstalk, particularly through myokines, has emerged as a fundamental aspect of nutrient and energy homeostasis. However, a comprehensive understanding of myokine biology in the setting of obesity and T2D remains a major challenge. In this review, we discuss the regulation and biological functions of key myokines that have been extensively studied during the past two decades, namely interleukin 6 (IL-6), irisin, myostatin (MSTN), growth differentiation factor 11 (GDF11), fibroblast growth factor 21 (FGF21), apelin, brain-derived neurotrophic factor (BDNF), meteorin-like (Metrnl), secreted protein acidic and rich in cysteine (SPARC), β-aminoisobutyric acid (BAIBA), Musclin, and Dickkopf 3 (Dkk3). Related to these, we detail the role of exercise in myokine expression and secretion together with their contributions to metabolic physiology and disease. Despite significant advancements in myokine research, many myokines remain challenging to measure accurately and investigate thoroughly. Hence, new research techniques and detection methods should be developed and rigorously tested. Therefore, developing a comprehensive perspective on myokine biology is crucial, as this will likely offer new insights into the pathophysiological mechanisms underlying obesity and T2D and may reveal novel targets for therapeutic interventions.

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Figure 1 Milestones in myokine research. From the hypothesis of the humoral hypoglycemic factor in 1961, muscle-secreted factors, namely myokines, have been studied intensely over the past century. The classification of IL-6 as the first myokine was initially completed by the identification of its muscle source and corresponding biological effects. This led to the research on other novel myokines. IL-6, interleukin 6; MSTN, myostatin; GDF11, growth differentiation factor 11; Metrnl, meteorin-like; SPARC, secreted protein acidic and rich in cysteine; BAIBA, β-aminoisobutyric acid; FGF21, fibroblast growth factor 21; Dkk3, Dickkopf 3; BDNF, brain-derived neurotrophic factor. Created with BioRender.com.
Figure 1 Milestones in myokine research. From the hypothesis of the humoral hypoglycemic factor in 1961, muscle-secreted factors, namely myokines, have been studied intensely over the past century. The classification of IL-6 as the first myokine was initially completed by the identification of its muscle source and corresponding biological effects. This led to the research on other novel myokines. IL-6, interleukin 6; MSTN, myostatin; GDF11, growth differentiation factor 11; Metrnl, meteorin-like; SPARC, secreted protein acidic and rich in cysteine; BAIBA, β-aminoisobutyric acid; FGF21, fibroblast growth factor 21; Dkk3, Dickkopf 3; BDNF, brain-derived neurotrophic factor. Created with BioRender.com.CC BY · PubMed Central
Figure 2 Metabolic effects of myokines on organs. Schematic diagram summarizing the main metabolic effects of IL-6, irisin, MSTN, GDF11, FGF21, apelin, BDNF, Metrnl, SPARC, BAIBA, Musclin, and Dkk3 on organs, including skeletal muscle, adipose tissue, liver, pancreatic islets. These myokines are secreted by skeletal muscle cells, which then act on organs, participating in the regulation of energy expenditure and metabolism. In terms of specific effects, the dotted line indicates speculation and/or controversy. BAT, brown adipose tissue; WAT, white adipose tissue. Created with BioRender.com.
Figure 2 Metabolic effects of myokines on organs. Schematic diagram summarizing the main metabolic effects of IL-6, irisin, MSTN, GDF11, FGF21, apelin, BDNF, Metrnl, SPARC, BAIBA, Musclin, and Dkk3 on organs, including skeletal muscle, adipose tissue, liver, pancreatic islets. These myokines are secreted by skeletal muscle cells, which then act on organs, participating in the regulation of energy expenditure and metabolism. In terms of specific effects, the dotted line indicates speculation and/or controversy. BAT, brown adipose tissue; WAT, white adipose tissue. Created with BioRender.com.CC BY · PubMed Central
Figure 3 Physical exercise mediates the regulation of myokines. Schematic diagram of physical exercise-mediated regulation of myokine expression levels, summarizing the effects of exercise on major metabolic organs, including adipose tissues, skeletal muscle, β-cells, and liver. The levels of IL-6, apelin, irisin, GDF11, Metrnl, SPARC, FGF21, BDNF, and BAIBA increase after exercise, and the level of MSTN decreases after exercise. Notably, the level of Musclin has been reported to increase or decrease upon exercise depending on the experimental conditions. MSTN, myostatin; BAT, brown adipose tissue; WAT, white adipose tissue. Created with BioRender.com.
Figure 3 Physical exercise mediates the regulation of myokines. Schematic diagram of physical exercise-mediated regulation of myokine expression levels, summarizing the effects of exercise on major metabolic organs, including adipose tissues, skeletal muscle, β-cells, and liver. The levels of IL-6, apelin, irisin, GDF11, Metrnl, SPARC, FGF21, BDNF, and BAIBA increase after exercise, and the level of MSTN decreases after exercise. Notably, the level of Musclin has been reported to increase or decrease upon exercise depending on the experimental conditions. MSTN, myostatin; BAT, brown adipose tissue; WAT, white adipose tissue. Created with BioRender.com.CC BY · PubMed Central

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Metadata

Authors
Chen, Z.-T., Weng, Z.-X., Lin, J. D., & Meng, Z.-X.
Affiliations
  • Second Affiliated Hospital of Zhejiang University (CN)
  • University of Michigan (US)
  • Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine (CN)
Corresponding author
  • Lin, Jiandie D
  • Meng, Zhuo-Xian
ORCID
Venue
Life Metabolism
Publisher
Oxford University Press (OUP)
Published
2024-03-02
Volume
3
Issue
3
Pages
loae006-loae006
ISSN
2755-0230 (ISSN-L)
DOI
10.1093/lifemeta/loae006
PMC
PMC11749576
OpenAlex
W4392351638
Cited by
58
References
346
Citations by year
2026: 29 · 2025: 27 · 2024: 2
FWCI
3.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Life Metabolism (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Key Research and Development Program of China (2018YFA0800403, 2021YFC2701903)
  • National Natural Science Foundation of China (91857110, 81670740, 32000817, 82100904, 82300910)
  • National Outstanding Youth Science Fund Project of National Natural Science Foundation of China (81722012)
  • Zhejiang Provincial Natural Science Foundation of China (LZ21H070001, LHDMD22H02001, LHDMD24H030001)
  • Innovative Institute of Basic Medical Sciences of Zhejiang University
  • Fundamental Research Funds
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
myokines, skeletal muscle, obesity, type 2 diabetes, interleukin-6, irisin, myostatin, GDF11, FGF21, apelin, brain-derived neurotrophic factor, Metrnl, SPARC, musclin, Dickkopf-3, physical activity, organ crosstalk, energy homeostasis, metabolic regulation

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