Secretory Function of Skeletal Muscle: Research on Systemic Metabolic Regulation by Myokines

Preface: A Scientific Bridge from the Laboratory to Taiwan’s Roads

Skeletal muscle has long been viewed as a mere “locomotive organ,” but the endocrinology revolution of the past two decades has given it a new identity: the body’s largest endocrine organ. During exercise, contracting muscles secrete hundreds of signaling molecules—myokines—that enter the bloodstream and issue commands to adipose tissue, the liver, bones, the pancreas, and the brain, coordinating whole-body metabolism. This explains why the benefits of exercise extend throughout the body. This article will introduce you to muscle as an underappreciated “endocrine factory.”

Muscle as an Endocrine Organ

The Pedersen team established the secretory function of skeletal muscle: contracting muscle fibers release a “secretome” composed of proteins, peptides, and metabolites, collectively termed myokines. These molecules operate via autocrine (acting on the muscle itself), paracrine (adjacent tissues), and endocrine (distant organs) mechanisms. The discovery of myokines redefined exercise—it is not merely energy expenditure but a systemic endocrine dialogue, with muscle as the primary voice. This also explains why “muscle mass” is highly correlated with metabolic health and longevity.

Star Myokines and Their Cross-Organ Effects

Representative myokines include: IL-6 (acute anti-inflammatory, promotes lipolysis and glucose metabolism), irisin (promotes white adipose browning, increases thermogenesis and energy expenditure), BDNF (supports neuroplasticity), SPARC (potential anti-cancer effects), IL-15 (regulates muscle–adipose crosstalk), and myostatin (negatively regulates muscle growth; exercise suppresses it). Their effects on adipose tissue, the liver, bone, the brain, the pancreas, and the immune system constitute the molecular network underlying the systemic benefits of exercise—the molecular footnote to “exercise is medicine.”

Muscle–Organ Crosstalk and Clinical Significance

Myokine-mediated muscle–organ crosstalk has major clinical implications: muscle secretions improve insulin sensitivity (countering diabetes), promote fat metabolism (countering obesity), influence bone metabolism (countering osteoporosis), and support brain health (countering cognitive decline). Conversely, loss of muscle mass (e.g., sarcopenia, sedentary behavior) reduces this beneficial secretion, accelerating metabolic deterioration. This reinforces the concept that “maintaining muscle mass = maintaining metabolic health”—resistance training is not just about building strength; it is the switch that activates endocrine benefits.

Irisin and Adipose Browning: The Endocrine Mechanism of Exercise-Induced Fat Burning

Irisin is one of the most prominent myokines, discovered by Boström et al. (2012, Nature). During exercise, muscle secretes irisin under the drive of PGC-1α, promoting “browning” of white adipose tissue—conferring brown-adipose-like thermogenic properties on energy-storing white adipocytes, thereby increasing energy expenditure and metabolic rate. This muscle–adipose endocrine axis provides a molecular explanation for the fat-burning benefits of exercise: exercise does not merely burn calories in the moment; through irisin, it “directs” adipose tissue to maintain elevated metabolic activity over the long term. Although the exact role of irisin in humans remains a subject of academic debate (early antibody specificity was questioned), the concept of the muscle–adipose browning axis has gained broad support and is an important mechanism for understanding the metabolic benefits of exercise and combating obesity.

The Link Between Muscle Mass, Sarcopenia, and Metabolic Health

Myokine research reinforces the concept that “muscle mass is a metabolic asset.” Adequate muscle mass means more active myokine secretion, supporting whole-body metabolic health; conversely, muscle loss (sarcopenia) weakens this beneficial secretion, accelerating metabolic deterioration and creating a vicious cycle. In older adults, sarcopenia often coexists with obesity (sarcopenic obesity), carrying particularly high metabolic risk. This explains why maintaining muscle mass is so critical for metabolic health—it is not merely a matter of strength but an endocrine issue. Combating sarcopenia requires resistance training (stimulating muscle protein synthesis and myokine secretion) combined with adequate protein intake (providing the raw materials). This is an important health message for Taiwan’s aging population and sedentary office workers: building muscle is maintaining an endocrine system that protects the entire body.

The Complexity of Myokine Research: The Case of Irisin

Myokine research is exciting but not without scientific controversy, and irisin is a prime example. After its publication in Nature in 2012, irisin sparked a wave of enthusiasm, but subsequent studies questioned the specificity of the antibodies used in early detection, briefly triggering a debate over whether irisin truly exists; later, more rigorous mass spectrometry methods confirmed the presence of circulating irisin in humans, but its exact physiological role and concentrations in humans remain under discussion. This case serves as a reminder: from “preliminary report” to “established function,” newly discovered molecules require rigorous methodological validation and time, and one should not jump to conclusions about the function of any single myokine. Nevertheless, the core paradigm—that muscle is an endocrine organ secreting multiple signaling molecules that coordinate the whole body—has gained broad support. A rational perspective: the overarching direction of the myokine field is credible, but the specific roles of individual molecules (such as irisin) are still being clarified; new findings should be viewed with cautious optimism rather than hype.

An Interdisciplinary Perspective: The Paradigm Shift in Muscle Endocrinology

Research on the secretory function of skeletal muscle represents a paradigm shift in exercise science—redefining muscle from a mere “locomotive organ” to “the body’s largest endocrine organ.” The discovery of myokines reveals that during exercise, muscle secretes hundreds of signaling molecules that coordinate whole-body metabolism across adipose tissue, the liver, bone, the brain, the pancreas, and the immune system. The revolutionary nature of this interdisciplinary integration (endocrinology, exercise physiology, metabolic science) lies in its explanation of why the benefits of exercise are so broad and systemic. From an endocrine perspective, muscle is an organ that secretes signals; from a metabolic perspective, myokines improve insulin sensitivity and promote fat metabolism; from a cross-organ perspective, muscle communicates with other organs through signaling. This viewpoint has fundamentally transformed our understanding of “exercise benefits” and “muscle mass”—maintaining muscle mass is not just for strength but for sustaining an endocrine system that protects the entire body. It provides a new mechanistic framework for combating metabolic syndrome, diabetes, and sarcopenia: exercise improves metabolism at its root through the endocrine function of muscle. Understanding muscle endocrinology allows us to view “building muscle” from an entirely new height—as the endocrine switch that activates whole-body health.

From Research to the Training Floor: An Action Framework for Activating Muscle Endocrinology

Activating the endocrine benefits of muscle can be approached through the framework of “maintain muscle mass—combine aerobic and resistance training—avoid sedentary behavior—consume adequate protein.” Maintain muscle mass: muscle mass is a metabolic asset; adequate muscle mass means more active myokine secretion; combating sarcopenia (especially in middle-aged and older adults) is not just for strength but for sustaining the endocrine network that protects adipose tissue, bone, and the brain. Combine aerobic and resistance training: different exercises induce different myokines—aerobic exercise strongly induces IL-6, irisin, and others, while resistance training stimulates muscle protein synthesis and myokine secretion and maintains muscle mass; the combination of both yields the most comprehensive benefits. Avoid sedentary behavior: activating the endocrine function of muscle requires muscle contraction; prolonged sitting shuts down this beneficial secretion; regular exercise plus reduced sitting time (getting up and moving periodically) is needed to continuously trigger myokines. Consume adequate protein: provide the raw materials for muscle maintenance and synthesis (approximately 1.6–2.2 g per kilogram of body weight, distributed across meals). For the prevention and management of metabolic syndrome, diabetes, and sarcopenia in Taiwan, this framework is particularly important, and resistance training is a critical gap overlooked by many—especially older adults and women. The core message: by maintaining muscle mass and engaging in regular aerobic plus resistance exercise, you activate and sustain this endocrine system of muscle that protects the entire body.

Local Applications in Taiwan: Climate, Events, and Cultural Context

The prevalence of metabolic syndrome and type 2 diabetes in Taiwan makes myokine research a powerful argument for exercise prescription: exercise is not just about “burning calories”—it fundamentally improves metabolism through signaling molecules secreted by muscles. This is especially important for sedentary office workers—activating the endocrine function of muscles requires muscle contraction, and regular exercise (especially combining resistance training to maintain muscle mass) is the only switch. Under Taiwan’s aging population, sarcopenia prevention also gains a new perspective: maintaining muscle mass is not just for strength, but for sustaining this endocrine system that protects the entire body. Encouraging the public to “build muscle” is a vital part of preventive medicine.

Metabolic syndrome and diabetes are prevalent in Taiwan, yet many people (especially the elderly and women) neglect resistance training. Myokine research provides a compelling argument: maintaining muscle mass is key to systemic metabolic health. Resistance training is not just about building strength—it activates endocrine benefits that protect fat, bone, and the brain. Encouraging the public to “build muscle” is a critical gap in Taiwan’s preventive medicine.

Frequently Asked Questions and Myth Clarification

Myth 1: Can supplementing with irisin help you burn fat and lose weight? There is currently no safe or effective way to supplement irisin, and its effects in humans are still under investigation. Naturally stimulating its secretion through exercise is the right approach.

Myth 2: If you do aerobic exercise, you don’t need to build muscle? Wrong. Maintaining muscle mass is crucial for metabolic health—myokines secreted by muscles protect fat, bone, and the brain. Aerobic and resistance training should be given equal emphasis.

Myth 3: Can muscle hormones be made into a pill that replaces the benefits of exercise? Not yet. Exercise triggers a coordinated symphony of multiple myokines that is difficult to replicate with a single drug.

How to Read Exercise Science Research: Developing Evidence Literacy

This article cites four studies from top international journals (such as Journal of Applied Physiology, Medicine & Science in Sports & Exercise, Sports Medicine, Nature, and Cell series), but as a reader, cultivating “evidence literacy” can help you absorb this knowledge more rationally rather than accepting it at face value. First, distinguish study types: randomized controlled trials (RCTs) have the strongest causal inference, observational studies (cohort, cross-sectional) can only show associations rather than causation, and animal and cell studies reveal mechanisms but require caution when translating to humans. Second, pay attention to samples and contexts: results from small samples or specific populations (such as elite athletes or specific age groups) may not apply to you; studies based mainly on European and American populations also need scrutiny regarding their applicability to Taiwanese populations. Third, value effect size rather than just looking at “statistical significance”: statistical significance does not equal a practically meaningful benefit—ask “is this difference important in real training or health terms?” Fourth, be wary of over-extrapolation and commercialization: preliminary findings from a single study are often exaggerated into “miracle” products or methods; wait for replication and systematic reviews. Fifth, judge comprehensively based on the “consistency” of mechanistic, associative, and interventional evidence, rather than rejecting everything because of one study’s flaws or accepting everything because of one striking result. Sixth, understand that “individual variability” is the norm in exercise science: the same intervention produces different responses in different people due to genetics, training background, lifestyle, and environment; research presents group averages, so when applying findings to yourself, be sure to observe your own actual responses and adjust accordingly. Seventh, prioritize the “fundamentals”: sleep, nutrition, regular training, and recovery—these have overwhelming evidence and clear benefits—are always worth investing in before any novel supplements, equipment, or methods. Many seemingly sophisticated interventions offer marginal benefits far smaller than getting the basics right. Exercise science is a constantly evolving field; maintaining an open yet critical attitude, updating your knowledge as evidence evolves, respecting individual variability, and valuing the fundamentals are what allow you to truly translate cutting-edge research from international journals into training and health decisions that are useful, safe, and sustainable in the long term—rather than blindly following trends or deferring to a single authority.

Key Takeaways

Synthesizing the interdisciplinary research and mechanistic analyses above, the core points can be distilled as follows: Muscles are endocrine organs: the systemic benefits of exercise come from signaling molecules secreted by muscles. Maintaining muscle mass = maintaining metabolic health: resistance training activates beneficial endocrine functions. Sedentary behavior shuts down muscle secretion: regular contraction is required to trigger the protective effects of myokines. Combating sarcopenia has dual significance: preserving strength and preserving systemic metabolic regulation. Aerobic + resistance training should be equally emphasized: different exercises induce different myokines, and the combined benefits are the most comprehensive. Behind these points lies the convergence of multiple fields—sleep science, immunology, genomics, neuroscience, microbiology, endocrinology, and data science—which together convey a core message: the benefits and adaptations of exercise are the integrated result of multiple body systems working in coordination, not something a single factor can encompass. Understanding this interdisciplinary, integrative perspective helps us move beyond fragmented “treat-the-symptom” thinking and approach training, recovery, and health more holistically. Only by incorporating these principles into daily training and life, and dynamically adjusting them according to individual conditions, actual responses, and professional advice, can we translate cutting-edge findings from top international journals into practices that are truly feasible, safe, and sustainable within Taiwan’s climate, events, and lifestyle context. The value of exercise science ultimately lies in helping every athlete—elite or amateur, young or old—exercise smarter, healthier, and with more enjoyment, achieving physical and mental growth in the process.

Practical Recommendations for Taiwanese Athletes

1. Muscles are endocrine organs: The systemic benefits of exercise come from signaling molecules secreted by muscles.
2. Maintaining muscle mass = maintaining metabolic health: Resistance training activates beneficial endocrine functions.
3. Sedentary behavior shuts down muscle secretion: Regular contraction is required to trigger the protective effects of myokines.
4. Combating sarcopenia has dual significance: Preserving strength and preserving systemic metabolic regulation.
5. Aerobic + resistance training should be equally emphasized: Different exercises induce different myokines, and the combined benefits are the most comprehensive.

Research Citations and Further Reading

• Pedersen, B. K., & Febbraio, M. A. (2012). Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nature Reviews Endocrinology, 8(8), 457–465.
• Boström, P., et al. (2012). A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis (irisin). Nature, 481, 463–468.
• Pedersen, B. K. (2011). Muscles and their myokines. Journal of Experimental Biology, 214(2), 337–346.
• Severinsen, M. C. K., & Pedersen, B. K. (2020). Muscle-organ crosstalk: the emerging roles of myokines. Endocrine Reviews, 41(4), 594–609.

This article is a translation of exercise science knowledge. Individual physiological responses vary. Please consult professional coaches and sports medicine physicians before making any training or intervention changes, and proceed gradually according to your personal health status.

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• Exercise and Hormones Fully Explained: Testosterone, Cortisol, and Growth Hormone—Understanding Your Endocrine Signals
• The Dual Role of Inflammatory Signals in Training Adaptation: Research on the Acute vs. Chronic Benefits of IL-6