Deeper Dive: Myokines and Muscle Receptors
Reviewed by Dr. Peter Rawlek, MD, Dr. Valena Wright, MD and Dr. Scott Rollo, PhD
When muscle contracts, it does more than move your body. It releases small signalling molecules called myokines. Think of myokines as messages sent out by active muscle.
These messages are not all the same. Different myokines carry different instructions, and different tissues have different “receivers,” called receptors, that respond to those messages. Some signals help muscle take in blood sugar. Some help regulate inflammation. Some communicate with fat tissue, the liver, blood vessels, the gut, and even the brain.
This is why active muscle is now understood as an endocrine organ, meaning it sends signals that influence other parts of the body. A frequently activated muscle is not just stronger. It becomes better at helping the body manage energy, inflammation, and repair.
The key point is simple. Muscle has to be used to send these signals. With each walk, climb, squat, jump, or short activity burst, muscles release messages that help the body work more efficiently. When muscle sits inactive for hours, that signalling system quiets down.
This is why small bouts of activity matter. Five minutes is not “nothing.” It is a signal. It turns the system on.
In summary:
Myokines are not one message. They are a whole messaging system. Different myokines carry different instructions, and different tissues respond depending on the receptors they carry. That is why regularly active muscle repeated small bouts throughout the day will influence blood sugar, inflammation, gut function, brain health, and long-term metabolic health.
Leading Reviews to Check:
Severinsen, M. C. K., & Pedersen, B. K. (2020). Muscle–organ crosstalk: The emerging roles of myokines. Endocrine Reviews, 41(4), 594–609.
Best broad review. Very useful for muscle communicating with brain, liver, gut, pancreas, adipose tissue, bone, vascular tissue, skin, and immune system.
Gao, X., et al. (2024). Unlocking the potential of exercise: Harnessing myokines for brain health and disease prevention. Frontiers in Physiology.
Useful for brain related signalling, including BDNF, irisin, IGF-1, CTSB, IL-6, and LIF.
Iglesias, P., et al. (2025). From skeletal muscle hormone regulation to myokine expression and function. Journal of Clinical Medicine.
Good newer review on muscle as both a target of hormones and a source of bioactive peptides with local and whole body effects.
Zunner, B. E. M., et al. (2022). Myokines and resistance training: A narrative review. International Journal of Molecular Sciences.
Helpful if you want to discuss resistance training and specific myokine responses.
Piccirillo, R. (2019). Exercise-induced myokines with therapeutic potential for muscle wasting. Frontiers in Physiology.
Clearly articulates the idea that different exercise induced myokines may have different therapeutic roles.
