Victor Forge
The endocrine system is made up of tissues that create and release hormones, such as the pituitary gland and thyroid. Certain organs in the body also produce and release hormones, including the liver, kidneys, and testes. Skeletal muscle has been identified as an endocrine organ due to its ability to secrete myokines, which are proteins released by muscle cells in response to contractions. These myokines have endocrine roles in exercise-induced adaptations, such as muscle hypertrophy and cancer protection, and can act as endocrine signaling mediators. The secretion of myokines by skeletal muscle can also initiate crosstalk with other tissues, including the brain, and improve a broad range of brain functions.
| Characteristics | Values |
|---|---|
| Skeletal muscle as an endocrine organ | The endocrine property of muscle cells is illustrated by the release of cytokines (e.g. IL-6) or metabolites (e.g. lactate) |
| Myokines | Proteins released by muscle cells in response to contractions |
| Myokine functions | Protect the functionality and enhance the exercise capacity of skeletal muscle |
| Myokine control | Adaptive processes in skeletal muscle by acting as paracrine regulators of fuel oxidation, hypertrophy, angiogenesis, inflammatory processes, and regulation of the extracellular matrix |
| Endocrine functions attributed to myokines | Body weight regulation, low-grade inflammation, insulin sensitivity, suppression of tumor growth, and improvement of cognitive function |
| Muscle-brain crosstalk | Physical exercise activates specific cellular pathways in muscle cells |
| Muscle as a secretory organ | The secretion of myokines, protein hormones that can exert autocrine, paracrine, and long-distance endocrine effects |
| Myokines | Myostatin, LIF, IL-6, IL-7, BDNF, IGF-1, FGF-2, FSTL-1, and irisin |
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What You'll Learn
Skeletal muscle as an endocrine organ
Skeletal muscle has been identified as an endocrine organ that produces and releases cytokines, which are termed "myokines". As the largest organ in the human body, skeletal muscle is now understood to secrete proteins, specifically myokines, in response to contraction. This discovery has established a link between skeletal muscle contractile activity and immune changes, as well as metabolic changes in other organs such as the liver and adipose tissue.
The major physiological function of the secretory capability of skeletal muscle is to protect and improve the functionality of the working muscle by regulating the intramuscular cross-talk of myofibers, immune cells, fibroblasts, the vasculature, and the bone. Myokines, released by muscle cells in response to contractions, play a crucial role in this process. They have autocrine, paracrine, and endocrine functions, contributing to various exercise-induced adaptations, including muscle hypertrophy and cancer protection.
The endocrine functions attributed to myokines have a wide range of beneficial effects on the body. They are involved in body weight regulation, low-grade inflammation, insulin sensitivity, suppression of tumor growth, and improvement of cognitive function. Additionally, myokines may exert a balancing effect on adipokines, which are cytokines produced by adipose tissue. This interplay between adipokines and myokines represents a yin-yang balance in the body.
The identification of skeletal muscle as an endocrine organ has significant implications for our understanding of the nervous, endocrine, and immune systems, especially in maintaining homeostasis during periods of increased energy demands. Furthermore, it provides a new perspective on the health-promoting effects of exercise, as the factors secreted by skeletal muscle act as endocrine signaling mediators, influencing almost all cell types and organs.
While the secretome of exercising skeletal muscle has not yet been fully described, it is known to consist of proteins, peptides, metabolites, lipids, and RNA molecules. These factors can act as muscle-derived paracrine or endocrine factors, termed "myometabokines," and contribute to the beneficial effects of exercise by activating surface or intracellular receptors.
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Myokines and their role in exercise adaptations
Skeletal muscle behaves as an endocrine organ by secreting myokines, which are proteins released by muscle cells in response to contractions. Myokines are involved in exercise-induced adaptations and modulate the function of metabolic organs in response to exercise. They have autocrine, paracrine, and endocrine roles in several exercise-induced adaptations, such as muscle hypertrophy, cancer protection, and cognitive function.
The discovery of interleukin (IL)-6 release from contracting skeletal muscle has led to the identification of myokines and their role in exercise adaptations. IL-6 is a myokine with endocrine effects, and it also works in a paracrine manner, exerting metabolic effects within the muscle itself. The muscular expression of the IL-6 receptor (IL-6R) is elevated in trained human muscle, indicating that muscular sensitivity to IL-6 is increased by training adaptation. IL-6 signalling within the muscle can affect glucose uptake and fat oxidation, as well as increasing both basal glucose uptake and glucose transporter GLUT4 translocation.
The secretion of myokines by skeletal muscle initiates a crosstalk with other tissues, including the liver, fat, and the brain. This crosstalk results in the coordination of exercise-induced adaptations in these organs. For example, PGC-1α activation in skeletal muscle induces the expression of FNDC5, which is cleaved to irisin and released into the circulation. Irisin is an exercise-induced myokine that has been shown to activate brown fat function in humans.
Additionally, myokines can act as biomarkers for monitoring the type and amount of exercise required for individuals with specific conditions, such as cancer, diabetes, or neurodegenerative diseases. The identification of new myokines and their specific roles may lead to novel therapeutic targets. Furthermore, understanding the role of the muscle secretome in controlling appetite and energy intake is an important area of research, as physical activity is known to influence these factors.
In summary, myokines play a crucial role in exercise adaptations by regulating processes within the muscle itself and coordinating adaptations in other organs through endocrine crosstalk. Further research is needed to fully characterise the respective roles of each myokine and their potential synergistic contributions to exercise adaptations.
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Interplay between adipokines and myokines
Skeletal muscle and adipose tissue are the two largest organs in the body. Skeletal muscle is an effector organ, while adipose tissue is an energy reserve organ. Both are endocrine organs that secrete cytokines, namely myokines and adipokines, respectively.
Myokines are proteins released by muscle cells in response to contractions. They have autocrine, paracrine, and endocrine roles in many exercise-induced adaptations, such as muscle hypertrophy and cancer protection. Adipokines, on the other hand, are secreted by adipose tissue and play a role in regulating energy homeostasis and fat distribution.
The interplay between adipokines and myokines is complex and has important implications for processes such as lipolysis control, insulin sensitivity, and the prevention of obesity-driven chronic low-grade inflammation. This interplay is further influenced by exercise, which modulates the release of myokines and adipokines, leading to beneficial health effects. For example, acute exercise bouts appear to stimulate the release of myokines, while chronic exercise training correlates with changes in basal circulating adipokines, possibly associated with weight loss.
In addition, the secretion of certain cytokines, such as IL-6 and TNF-α, by both skeletal muscle and adipose tissue creates a complex endocrine interconnection between the two types of organs. This interconnection has been described as a yin-yang balance, reflecting the importance of the interplay between adipokines and myokines in maintaining overall health.
Furthermore, understanding the mechanisms connecting the interplay of adipokines and myokines is crucial in developing therapeutic strategies for cancer cachexia, a condition characterized by weight loss, metabolic abnormalities, and inflammation in cancer patients. The complex pathophysiology of cancer cachexia involves the interaction of various adipokines, myokines, and cytokines, which contribute to systemic inflammation and cancer progression.
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Muscle-brain crosstalk
Skeletal muscle is an endocrine organ that regulates energy homeostasis and coordinates exercise-induced adaptations in other organs, including the liver, fat, and brain. The secretion of myokines, protein hormones, and metabolites from contracting muscle cells mediates this muscle-initiated crosstalk with other tissues. Myokines, such as cathepsin B, can pass through the blood-brain barrier, influencing brain-derived neurotrophic factor production, neurogenesis, memory, and learning.
Exercise stimulates the release of myokines, which have autocrine, paracrine, and endocrine roles in exercise-induced adaptations. Myokines protect and enhance the functionality and exercise capacity of skeletal muscle by regulating intramuscular crosstalk among myofibers, immune cells, fibroblasts, vasculature, and bone. They also contribute to body weight regulation, insulin sensitivity, and cognitive function.
Additionally, there is evidence of a bidirectional influence between circadian and exercise pathways in muscle cells, although its significance for skeletal muscle endocrine function requires further investigation. The circadian clock provides a molecular basis for timely endocrine signaling, suggesting that time-based physical activity interventions may maximize the health benefits of exercise.
The muscle secretome, which includes proteins, peptides, metabolites, lipids, and RNA molecules, contributes to the health-promoting effects of exercise. However, the entire secretome of exercising skeletal muscle has not yet been fully described, and the molecular and cellular mechanisms underlying muscle-brain communication remain incompletely understood.
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Muscle as an immunogenic organ
Skeletal muscle has been identified as an immunogenic organ, with a possible link between skeletal muscle contractile activity and immune changes. Exercise has been found to increase the number of cytokines, which are produced, expressed, and released by muscle fibers. These cytokines, along with other peptides, are classified as 'myokines' and exert either paracrine or endocrine effects. Human skeletal muscle can express several myokines, including interleukin (IL)-6, IL-8, and IL-15, which play a role in regulating cytokine expression in skeletal muscle. These myokines have possible anti-inflammatory, immunoregulatory, and metabolic roles.
The secretory capability of skeletal muscle is essential for protecting and improving the functionality of the working muscle. It does so by regulating the intramuscular cross-talk of myofibers, immune cells, fibroblasts, the vasculature, and the bone. The secretome of skeletal muscle comprises proteins and peptides, as well as metabolites and lipids. These factors can act as muscle-derived paracrine or endocrine factors, termed "myometabokines," and contribute to the health-promoting effects of exercise.
Myokines, released by muscle cells in response to contractions, have various endocrine roles in exercise-induced adaptations. They are involved in body weight regulation, low-grade inflammation, insulin sensitivity, suppression of tumor growth, and improvement of cognitive function. Exercise stimulates the release of myokines, which have endocrine functions and enhance the exercise capacity of skeletal muscle.
The endocrine property of muscle cells is further demonstrated by the release of cytokines, such as IL-6, and metabolites such as lactate. Additionally, the secretion of myokines by skeletal muscle initiates crosstalk with other tissues, including the liver, adipose tissue, and the brain. This crosstalk is achieved through the secretion of myokines, which can exert autocrine, paracrine, and long-distance endocrine effects. The muscle secretome, influenced by circadian clocks, may also play a role in maximizing the effects of exercise on brain physiology.
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Frequently asked questions
An endocrine organ is an organ that creates and releases hormones.
Yes, skeletal muscle is an endocrine organ. It releases myokines, which are proteins that are released by muscle cells in response to contractions.
Myokines have autocrine, paracrine, and endocrine functions. Their major physiological function is to protect and improve the functionality of the working muscle. They also enhance the exercise capacity of skeletal muscle and have been linked to body weight regulation, low-grade inflammation, insulin sensitivity, and improvement of cognitive function.
Exercise stimulates the release of myokines. Myokines may mediate the protective effects of muscular exercise and have been linked to the prevention and treatment of various pathologies.
Examples of myokines include myostatin, LIF, IL-6, IL-7, BDNF, IGF-1, FGF-2, FSTL-1, and irisin.
