Irisin
The exercise-released myokine that browns white fat and is linked to bone density and cognitive protection — a decade-long scientific brawl over whether it exists that has largely resolved in its favour.
Also known as FNDC5 cleavage product, exercise myokine, FNDC5(32-143)
Observational — Human data without randomisation. Suggestive, and easily confounded.
Strong and reproducible rodent data for adipose browning and bone effects, plus a large human observational literature correlating circulating irisin with fitness, bone density and metabolic health. Zero human interventional dosing studies. The 2012 discovery paper survived a decade of methodological attack and mass spectrometry ultimately confirmed the peptide is real in human plasma.
How it works
Exercise raises PGC-1-alpha, which induces FNDC5; the ectodomain is cleaved and glycosylated to release irisin into circulation. The receptor was identified as the integrin alpha-V/beta-5 complex, which finally gave the field a mechanism rather than a correlation. Downstream, irisin upregulates UCP1 in subcutaneous white adipose tissue, converting it toward a beige thermogenic phenotype, and acts on osteocytes to influence sclerostin and bone remodelling. Central effects on hippocampal BDNF have been reported, and irisin appears necessary for exercise-induced cognitive benefit in Alzheimer's mouse models. The long controversy came from bad antibodies producing non-specific bands in Western blots; mass-spectrometry work settled that human irisin is genuinely present in plasma and rises with exercise, though the absolute concentrations are far lower than the early ELISA studies claimed.
Targets: Integrin alpha-V/beta-5, UCP1, PGC-1-alpha axis, Sclerostin/osteocyte signalling, Hippocampal BDNF
Dosing
| Protocol | Dose | Frequency | Route |
|---|---|---|---|
| No established administration protocolNot applicable. | — | not established | subcutaneous |
- · Irisin is not administered therapeutically in humans anywhere. Recombinant irisin used in animal work is dosed by body weight intravenously or intraperitoneally. The practical way to raise irisin is resistance and high-intensity exercise, which is not a joke answer — it is the only validated intervention.
Cycling
Not applicable; no administration protocol exists.
Pharmacology
- Half-life
- Circulating half-life is short — on the order of an hour or less in rodents. Not characterised in humans.
- Onset
- Plasma levels rise acutely during and shortly after exercise; browning of adipose tissue in animal models takes 10 days or more of sustained exposure.
- Routes
- subcutaneous, intravenous
- Molecule
- Glycosylated myokine cleaved from the FNDC5 membrane protein
- Sequence length
- 112 amino acids
Handling
- Diluent
- Not applicable
- Lyophilised
- Freezer at -20 C or below; it is a protein, not a short peptide.
- Reconstituted
- Refrigerated for days at most, with carrier protein to prevent surface adsorption.
Mixing
Recombinant irisin sold to labs is a glycoprotein produced in mammalian or insect cells, not a solid-phase synthetic peptide. Anything marketed as cheap 'synthetic irisin' in a peptide vial is almost certainly not correctly glycosylated and therefore not bioactive.
Side effects
- commonUnknown in humans— No human administration studies have been done, so there is no side-effect profile to report.
Do not use if
- Human self-administration generally — recombinant glycoproteins from unregulated sources carry real immunogenicity and endotoxin risk.
What to monitor
- · Serum irisin assays are notoriously unreliable between kits; do not chase the number.
Legal status
Research reagent only. Not approved, not scheduled, not sold as a therapeutic anywhere.
References
- Bostrom et al. 2012, Nature — PGC1-alpha-dependent myokine irisin drives browning of white fat (preclinical)
- Kim et al. 2018, Cell — integrin alpha-V/beta-5 identified as the irisin receptor (preclinical)
Mechanism in depth
A cleavage product of the membrane protein FNDC5, released from muscle during exercise, proposed to drive browning of white adipose tissue through UCP1 induction. Signalling is now attributed to integrin alpha-V/beta-5 receptors rather than an orphan receptor. The biology is real but the magnitude has been contested since the beginning.
What usually goes wrong
Irisin is the cautionary tale of the whole field. The initial human measurements were made with commercial ELISA kits whose antibodies were later shown to be non-specific, so a large body of literature reporting circulating irisin levels was measuring something else. Mass spectrometry subsequently confirmed that human irisin exists, but at concentrations far lower than the discredited assays reported. Any claim resting on an ELISA-based irisin level from that era should be treated as unmeasured.
Receptor targets
- Integrin alphaV/beta5 — Identified relatively recently; affinity data are limited
Proposed browning of white adipose tissue and bone effects
Genuinely uncertain
- Whether circulating irisin reaches concentrations sufficient to drive adipose browning in humans is genuinely unresolved.
- Much of the pre-2015 human literature used antibodies later shown to be non-specific.
- No therapeutic irisin product exists; anything sold under the name is unvalidated.