Your muscles are an endocrine organ: what “myokines” actually do

For most of the last century, skeletal muscle was treated as a motor — tissue that pulls on bones and burns fuel to do it. Over the past two decades that picture has been rewritten. In a landmark 2012 review in Nature Reviews Endocrinology, Bente Pedersen and Mark Febbraio set out the case that skeletal muscle is a secretory organ: an endocrine tissue that releases signalling molecules into the bloodstream every time it contracts. That reframing changes how we should think about why movement protects health.

What a myokine actually is

Pedersen and Febbraio proposed the term myokine for the cytokines and other peptides that are produced, expressed and released by muscle fibres and then exert autocrine, paracrine or endocrine effects. Autocrine means the molecule acts back on the muscle that made it; paracrine, on neighbouring tissue; endocrine, on distant organs via the blood. The scale is striking: the review noted that the muscle “secretome” consists of several hundred secreted peptides — not a handful of molecules but an entire signalling repertoire.

This gives, in the authors’ words, a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs — including adipose tissue, liver, pancreas, bone and brain. A contracting muscle is not just consuming energy; it is broadcasting chemical messages across the body.

What individual myokines do

Some myokines act within the muscle itself: myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and the formation of new muscle fibres. Others reach far beyond it. BDNF and IL-6 are involved in AMPK-mediated fat oxidation — part of how exercise shifts the body toward burning fat. IL-6, released in large amounts during contraction, also has systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and the pancreatic islets that regulate blood sugar.

The review catalogued others too: the osteogenic factors IGF-1 and FGF-2, which support bone; FSTL-1, which improves the endothelial function of blood vessels; and the PGC-1α-dependent myokine irisin, which drives “brown-fat-like” development, nudging energy-storing white fat toward a more energy-burning phenotype. The authors also flagged evidence for still-unidentified factors that may influence cancer cell growth and pancreatic function.

Skeletal muscle is an endocrine organ that produces and releases myokines in response to contraction, which thereby regulate metabolism in tissues and organs.

Why inactivity is a metabolic problem

The crucial clinical point is that many of these proteins are dependent upon contraction. Muscle only sends most of these signals when it is used. Pedersen and Febbraio argued that physical inactivity therefore probably leads to an altered myokine response — which they proposed as a potential mechanism for the well-documented association between sedentary behaviour and a long list of chronic diseases. In other words, prolonged sitting may not just fail to help; it may silence a signalling system your metabolism depends on.

The practical takeaway

You don’t need to measure myokines to benefit from them. The mechanism explains something people feel but rarely articulate: the payoff from training extends far beyond the muscle you can see or the weight you can lift. Regular contraction — resistance work, brisk walking, anything that makes muscle do meaningful work — is what keeps this endocrine tissue talking to your fat, liver, pancreas, bone and brain.

Misi’s training and habit plans are built around consistent, progressive muscle use and around breaking up long sedentary stretches — not because strength is the only goal, but because an active, well-maintained muscle system is one of the most powerful metabolic levers you have.

Misi is a coaching and wellness platform, not a medical service, and this article is educational and not a substitute for personalised medical advice.