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Myokine: Definition, Key Examples and How They Are Measured

A myokine is a peptide or protein released by skeletal muscle. Definition, examples, myostatin, exercise findings and an assay checklist for lab staff.

Written and maintained by CASRAI Editorial Board

Last updated

General information for researchers and laboratory staff. This page is not medical or exercise advice.

Short answer

A myokine is a peptide or protein released by skeletal muscle cells that acts locally or reaches other tissues through the blood. One review describes myokines as “a group of cytokines, small peptides, and proteoglycan peptides, secreted by contracting skeletal muscle cells”. Examples include interleukin-6 (IL-6), irisin, myostatin, BDNF, follistatin and decorin. For bench work the practical issue is measurement: several myokine assays are contested.

Definition and scope

An editorial in the research literature defines a myokine narrowly as a peptide or protein secreted by skeletal muscle cells, which excludes metabolites and microRNAs. It adds that release does not have to depend on contraction, and credits Pedersen and colleagues with introducing the term in 2003. Myokines can act in a paracrine (neighbouring cells), autocrine (the muscle cell itself) or endocrine (distant organs) way.

The broader concept is the muscle secretome, which also includes microRNAs, mitochondrial DNA, metabolites, enzymes and extracellular vesicles. The same editorial notes that many factors identified in isolated muscle or animal models have not been replicated in humans, and that circulating levels vary widely.

Term What it covers (as used in the sources)
Myokine Peptide or protein secreted by skeletal muscle cells; local or circulating
Muscle secretome Myokines plus microRNAs, mtDNA, metabolites, enzymes and extracellular vesicles

What are the functions of myokines in skeletal muscle?

Functions reported in the resistance-training review differ by molecule, and the evidence is uneven:

  • Myostatin is a negative regulator of muscle growth.
  • Follistatin and decorin are described as myostatin antagonists.
  • IL-6 is often called pro-inflammatory, but IL-6 from working muscle is reported to have anti-inflammatory capacities and to be linked to insulin sensitivity and satellite cell activity.
  • Irisin has been proposed to induce browning of white adipose tissue.
  • BDNF rises after resistance training; the review states that BDNF cannot pass the blood-brain barrier.
  • Metrnl has been linked to adipose browning and glucose tolerance in mice.

What is meant by myostatin?

Myostatin is a myokine that acts as a negative regulator of muscle growth. The resistance-training review states that “myostatin is the only myokine that is reduced by exercise” and reports that a single resistance session reduced plasma and mRNA levels. That is the review’s own claim, so treat it as a reported finding rather than a universal rule. The same review notes that myostatin inhibition did not translate well from mouse to human.

What does the term “myokinetic” mean?

“Myokinetic” is not a standard term in the myokine reviews cited here, and it should not be read as a synonym for “myokine”. If you meet it in a source, check how that source defines it. The established term for muscle-derived signalling proteins is myokine.

Which exercises release myokines?

The resistance-training review reports the following, with the caveat that its included studies are “very heterogeneous”:

  • IL-6: the highest outputs came from full-body resistance workouts involving large muscle groups, though results across studies are described as controversial.
  • Irisin: most studies point to a positive effect of resistance exercise, with a possible advantage over aerobic exercise.
  • BDNF: circulating levels are elevated after resistance training, independent of the kind of resistance training.
  • Follistatin and decorin: increased plasma or serum levels are reported after resistance training.

The review concludes that the variety of exercise protocols and participants makes interpretation difficult and that no protocol can be recommended for an individual.

How myokines are measured: a checklist for lab staff

This checklist is drawn from the two sources below and is a prompt for study design, not a validated protocol.

  1. Check assay specificity. For irisin, the review says the formerly used commercial ELISA kits “seem to be rather unspecific”, and some kits cross-react with other proteins. Read the validation data for the exact kit and lot.
  2. Fix the sampling time. Irisin is short-lived, so different times of measurement after exercise lead to different conclusions. Record the interval between exercise and collection.
  3. State what was measured. Muscle biopsy mRNA and circulating protein are different readouts; the review reports both for myostatin.
  4. Report the exercise protocol and participant details. Protocol variety is the main reason studies are hard to compare. Small samples (9 to 10 participants in several studies) limit confidence.
  5. Handle specimens consistently. See the CASRAI entries on biospecimen, cryogenic sample storage and minus-80 freezer management, and on reproducibility for reporting.

Claim strength: what is better supported and what is contested

Topic How the sources frame it
Definition (protein or peptide from skeletal muscle) Stated in both sources
IL-6 from working muscle Reported as having anti-inflammatory capacities; results across studies described as controversial
Irisin Role described as still a topic of heated discussion; measurement disputed
Myostatin lowered by exercise Review’s claim from resistance-training studies; mouse-to-human translation of inhibition was poor
BDNF Rises after resistance training; does not cross the blood-brain barrier per the review
Animal and isolated-muscle findings Many not replicated in humans

Common misunderstandings

  • “Myokines are only released by contraction.” The editorial states release need not depend on contraction.
  • “A myokine is any signal from muscle.” Under the narrow definition metabolites and microRNAs are part of the secretome, not myokines.
  • “Myokine levels prove a training effect for an individual.” The review states no protocol can be recommended per person.

FAQ

What are the functions of myokines in skeletal muscle?

They signal locally and to other tissues. Reported roles include regulating muscle growth (myostatin, follistatin, decorin) and metabolic signalling (IL-6, irisin), with several findings still contested.

What does the term “myokinetic” mean?

It is not a standard term in the cited reviews. The accepted term is myokine.

What is meant by myostatin?

A myokine that negatively regulates muscle growth and is reported to fall after resistance exercise.

Which exercises release myokines?

Reviews report myokine changes after resistance and aerobic exercise; resistance training is the focus of the cited review, and protocol heterogeneity limits firm conclusions.

Sources

  • Myokines and Resistance Training: A Narrative Review. PubMed Central, PMC8998961. Read 2026-11-08.
  • Editorial: The Role of the Muscle Secretome in Health and Disease. PubMed Central, PMC7506065. Read 2026-11-08.

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