Myokines: The Secret Language of Your Muscles

2026-02-15

Your muscles are talking to you. Actually, they're talking to everything—your brain, your fat cells, your liver, your bones, even distant organs you didn't know were listening. And they're doing it through a sophisticated chemical language that scientists are only now beginning to decode.

Welcome to the world of myokines and exerkines—the molecular messengers that turn your skeletal muscle into the body's largest endocrine organ.

Your Muscles Are glands?!

For decades, we thought of muscle as simple: contract, relax, repeat. But research in the last 15 years has fundamentally rewritten that story. Skeletal muscle is now recognized as a dynamic endocrine organ that secretes hundreds of bioactive molecules—peptides, proteins, metabolites, and extracellular vesicles—collectively called myokines.

When you lift weights, your muscles don't just get shorter. They secrete these signaling molecules into your bloodstream, where they travel to tissues throughout your body, influencing metabolism, inflammation, brain function, and even cancer cell growth.

A landmark 2026 paper published in Cells described this as the "endocrine code" of skeletal muscle—a complex communication network that mediates virtually every beneficial effect of resistance training.

Key Myokines You Should Know

Irisin: The Fat-Burning Messenger

Perhaps the most famous myokine, irisin is released from muscle tissue during exercise, particularly aerobic and resistance training. It was discovered in 2012 and named after the Greek goddess Iris, the messenger.

Irisin's primary function: it signals to fat cells to brown—converting white adipose tissue (the stuff you want to lose) into beige/brite fat that burns calories for heat. Research shows irisin can increase energy expenditure by 15-20% in some studies.

But irisin does far more. A 2020 review in Endocrine Reviews found that irisin also:

Increases BDNF (brain-derived neurotrophic factor) in the brain
Improves cognitive function
Enhances bone density
Supports insulin sensitivity

The takeaway: that post-workout "glow" might literally be your muscles signaling fat to burn.

Interleukin-6 (IL-6): The Inflammation Regulator

IL-6 gained notoriety during COVID-19 as a marker of inflammation, but in the exercise context, it's actually anti-inflammatory. During muscle contractions, IL-6 is released and acts in a hormone-like fashion to:

Increase glucose uptake in muscles
Regulate glycogen breakdown for energy
Modulate immune response
Promote muscle repair

Interestingly, the IL-6 released during exercise is structurally different from the IL-6 associated with chronic inflammation. Acute exercise-induced IL-6 is transient and beneficial.

Myostatin: The Growth Brakes

Myostatin is a myokine that limits muscle growth. It's literally a "stop growing" signal. Mutations in the myostatin gene cause massive muscle hypertrophy in mice, cattle, and yes—even humans.

A child born with myostatin mutations (documented in a few rare cases) has dramatically increased muscle mass from birth. Pharmaceutical companies have been racing to develop myostatin inhibitors, with some showing promise for conditions like muscular dystrophy.

For natural lifters, the implication: your body has built-in limits on muscle growth, and myostatin is one of them. Training volume, sleep, and certain nutrients may help regulate myostatin expression.

Brain-Derived Neurotrophic Factor (BDNF): The Cognitive Connector

Your muscles produce BDNF, which crosses the blood-brain barrier and supports:

Neuroplasticity (learning and memory)
Neurogenesis (creation of new neurons)
Mood regulation
Protection against cognitive decline

This is the biological basis for the "runner's high" and why exercise improves mood and cognition. Your muscles are literally feeding your brain.

FGF21: The Metabolic Regulator

Fibroblast growth factor 21 (FGF21) is a stress-induced myokine that acts on the liver and fat tissue to:

Enhance insulin sensitivity
Promote fat oxidation
Improve glucose metabolism

FGF21 increases during endurance exercise and may be one reason why cardio improves metabolic health.

Exerkines: The Exercise "Secretome"

Beyond myokines (which are always present), exercise triggers the release of exerkines—a broader category of molecules released in response to exercise stress. These include:

Extracellular vesicles (tiny packages containing microRNAs that regulate gene expression)
Lactate (yes, lactate is a signaling molecule, not just a waste product)
β-aminoisobutyric acid (BAIBA) (promotes fat browning and reduces insulin resistance)

What This Means for Your Training

Understanding myokines explains why resistance training benefits everything—not just muscles. The systemic effects include:

Metabolic health: Improved insulin sensitivity, glucose regulation
Brain health: Better cognition, mood, neuroprotection
Fat loss: Direct signaling to burn fat through browning
Bone strength: Mechanical loading + myokine signaling
Anti-aging: Reduced inflammation, improved mitochondrial function
Cancer protection: A 2025 study found a single exercise session increased myokine levels that reduced cancer cell proliferation by 20-30%

Optimizing Your Myokine Response

How do you maximize this endocrine response? Research suggests:

Volume matters: Higher volume training (more sets, more total work) tends to produce greater myokine release than low-volume approaches. Mechanical tension is key: The muscle contraction itself drives secretion. Eccentric training may be particularly effective. Train large muscle groups: More muscle mass = more myokine production. Compound movements recruit more tissue. Consistency: Regular training leads to chronic elevation of beneficial myokines, not just acute spikes. Combine modalities: Both resistance and aerobic training produce distinct myokine profiles. Variety maximizes benefits. Sleep: Growth hormone and other hormones that interact with myokine pathways peak during deep sleep.

The Future: Myokine-Targeted Therapies

Pharmaceutical companies are actively developing myokine-based treatments. Companies are exploring:

Recombinant irisin for metabolic disorders
Myostatin inhibitors for muscle-wasting diseases
Exercise mimetic drugs that trigger myokine release

One day, you might be able to pop a pill that mimics the endocrine benefits of a workout. But until then, your muscles are already doing the work—all you need to do is train them.

Bottom Line

Your skeletal muscle isn't just a piece of meat hanging on your bones. It's a sophisticated communication hub, releasing molecular messages that influence virtually every system in your body. Every rep you do sends ripples through your endocrine system, improving not just your physique, but your brain, your metabolism, and your long-term health.

The next time you lift, remember: you're not just moving weight. You're running a chemical conversation that stretches from your muscles to your brain, your liver, your fat, and every cell in between.

That's not just a pump. That's a symphony.

References

Zarovni et al. (2026). "Decoding the Endocrine Code of Skeletal Muscle: Myokines, Exerkines, and Inter-Organ Crosstalk." Cells, 15(4), 318.
Pedersen & Febbraio. (2012). "Muscles, exercise and obesity: skeletal muscle as a secretory organ." Nature Reviews Endocrinology, 8, 457-465.
Bostrom et al. (2012). "A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis." Nature, 481, 463-468.
Wrann et al. (2013). "Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway." Cell Metabolism, 18(5), 649-659.
Bettariga et al. (2025). "Exercise-induced myokines and cancer cell proliferation." ScienceDaily.
Lee et al. (2020). "Muscle–Organ Crosstalk: The Emerging Roles of Myokines." Endocrine Reviews, 41(4), 594-608.