Meteorin-like (METRNL, also called Subfatin or IL-41) is a 311-amino-acid secreted protein that skeletal muscle releases after exercise and adipose tissue releases in the cold. It was identified in 2014 as one of the first molecular links between exercise and the "beiging" of white fat, and it has since turned out to be a ligand for the KIT receptor tyrosine kinase, a driver of post-infarction angiogenesis, and a candidate biomarker in type 2 diabetes. This profile covers the biology, what the human data support, and why it is a recombinant protein for cell and animal work rather than a synthesised research peptide.
> Research use only. METRNL is available only as a recombinant protein for in-vitro and preclinical investigation. It is not listed by any supplier on Peptides.SO, and nothing on this page is a protocol for human or animal administration.
Discovery: an exercise-induced hormone
METRNL was found by Bruce Spiegelman's laboratory using a muscle-specific PGC-1α isoform (PGC-1α4) as a discovery tool. The Cell paper Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis (PMID 24906147) reported that Metrnl is "induced in muscle after exercise and in adipose tissue upon cold exposure", that raising its circulating level in mice increased energy expenditure and improved glucose tolerance, and that the effect ran through an eosinophil-dependent rise in IL-4 and alternative activation of adipose tissue macrophages. Blocking Metrnl in vivo blunted the macrophage and thermogenic gene responses to chronic cold.
The companion paper in the same issue, Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat (PMID 24906148) from Ajay Chawla's laboratory, described the circuit Metrnl plugs into: eosinophils, IL-4/IL-13, and alternatively activated macrophages in cold-stressed subcutaneous white fat, with genetic loss of eosinophils or IL-4/13 signalling impairing cold-induced beige fat biogenesis. Read together, the two papers place Metrnl upstream of a type 2 immune circuit that was already known to be required for beiging.
The name comes from sequence similarity to Meteorin, a neurotrophic factor; the two share about 40% identity and Meteorin-like has no known neurotrophic role of its own.
Gene and protein
| Property | Value |
|---|---|
| Gene | METRNL, chromosome 17q25.3 (human); Metrnl on mouse chromosome 11 |
| Protein | 311 amino acids including a signal peptide; mature secreted form ~29–30 kDa |
| Aliases | Subfatin (from its high expression in subcutaneous fat), IL-41 |
| Receptor | KIT receptor tyrosine kinase (endothelial and immune cells); other receptors proposed but not confirmed |
| Main sources | Skeletal muscle (exercise), adipocytes (cold, differentiation), monocytes and macrophages, endothelium |
| Research format | Recombinant human or mouse protein, typically expressed in HEK293 or E. coli, supplied lyophilised with carrier protein |
METRNL is a glycosylated, disulfide-bonded protein, not a short peptide. It cannot be made by solid-phase synthesis at useful purity and is not part of the research-peptide supply chain. Suppliers are life-science reagent companies, and the relevant quality parameters are endotoxin level and bioactivity (typically an IL-4 induction or endothelial proliferation assay), not HPLC purity.
Mechanism
The eosinophil–IL-4–macrophage axis in adipose tissue
The original model, from the two 2014 Cell papers, is that Metrnl released by muscle or cold-exposed fat recruits or activates eosinophils in subcutaneous adipose tissue, eosinophils produce IL-4, and IL-4 drives adipose macrophages toward the alternatively activated (M2) state. Those macrophages produce catecholamines and other signals that induce UCP1 and the thermogenic programme in beige adipocytes. This is the pathway that explains the energy-expenditure and glucose-tolerance effects in mice.
A direct adipokine effect on insulin sensitivity
A second line of work treats Metrnl as an adipokine acting locally in fat. Adipocyte Metrnl Antagonizes Insulin Resistance Through PPARγ Signaling (PMID 26307585) used adipocyte-specific knockout and transgenic mice: loss of adipocyte Metrnl worsened high-fat-diet insulin resistance, while overexpression prevented insulin resistance induced by high-fat diet or leptin deletion. Body weight and fat mass were unchanged, and the authors found no correlation between serum Metrnl and BMI in humans. The mechanism was a pro-differentiation effect on white adipocytes through PPARγ, which is a different route from the immune circuit and does not require beiging.
KIT receptor ligand in the heart
The receptor question was open for eight years. Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase (PMID 35709278), published in Science in 2022, identified METRNL as a high-affinity ligand for KIT, the stem cell factor receptor. Monocyte- and macrophage-derived METRNL drove angiogenesis in cultured human endothelial cells through KIT-dependent signalling; in a mouse myocardial infarction model it expanded KIT-expressing endothelial cells in the infarct border zone, and Metrnl-deficient mice "failed to mount this KIT-dependent angiogenic response and developed severe postinfarction heart failure". This finding reframed METRNL from a metabolic hormone into a repair cytokine with a defined receptor, and it explains why the protein is now studied in ischaemic injury outside the heart as well.
Anti-inflammatory and pro-inflammatory roles
The 2026 review Meteorin-like/Metrnl: A pleiotropic cytokine implicated in metabolic, inflammatory and malignant disorders (PMID 41365208) is the current reference for the wider literature. It lists three unresolved contradictions: circulating Metrnl in type 2 diabetes and obesity "yield conflicting results"; the protein "exhibits a dual nature that is dependent on specific environments, with both anti-inflammatory and proinflammatory functions"; and while exercise-induced Metrnl produces metabolic benefits, CD8+ T-cell-derived Metrnl impairs anti-tumour immunity, which the authors flag as a concern for the exercise-cancer relationship. The 2014 papers alone give an incomplete picture of its inflammatory role.
Human data
Circulating levels in type 2 diabetes
Clinical studies of METRNL have almost all been cross-sectional serum measurements, and they do not agree. The 2025 meta-analysis Relationship between Meteorin-like protein and type 2 diabetes mellitus: an update and meta-analysis (PMID 40956671) pooled 17 studies (649 patients with type 2 diabetes, 396 controls) and found circulating Metrnl lower in diabetes with a standardised mean difference of −0.47 whose 95% confidence interval crossed zero (−0.98 to 0.05); restricting to serum rather than plasma gave a significant difference (SMD −0.91). The prediction intervals in both analyses were very wide, meaning individual studies point in both directions. An earlier meta-analysis had found no difference at all. Serum METRNL is probably somewhat lower in type 2 diabetes, that assay and matrix differences explain much of the variation, and that it is nowhere near a validated biomarker.
The 2022 review Meteorin-like protein (Metrnl): A metabolic syndrome biomarker and an exercise mediator (PMID 35780711) reaches the same conclusion from the broader metabolic-syndrome literature: Metrnl is regulated by obesity, diabetes, caloric restriction, weight loss and heart disease, "but due to the conflicting data yielded, Metrnl is still far from clinical application as a diagnostic and/or a therapeutic agent".
Exercise responses in humans
Human exercise studies have measured plasma METRNL before and after acute bouts and after training programmes. Results depend on the modality, the intensity and the assay, and the effect sizes are small relative to assay variability. No human study has administered METRNL, and there is no reason to expect one: it is a 30 kDa glycoprotein with no formulation or safety data.
Comparison with other exerkines
Irisin. The other muscle-derived beiging factor from the Spiegelman laboratory, cleaved from FNDC5. Irisin acts directly on adipocytes; METRNL acts through the immune system. Irisin's human relevance has been argued over antibody specificity for a decade; METRNL's assays have similar problems. See the irisin research profile.
FGF21. A liver- and muscle-derived hormone with a well-characterised receptor complex (FGFR1c/β-Klotho) and drug analogues in clinical trials. FGF21 is where the exerkine field has advanced furthest pharmacologically; METRNL is at the target-identification stage.
IL-6. The prototype myokine, released from contracting muscle in large amounts. IL-6's exercise biology is well mapped but its pro-inflammatory roles elsewhere have kept it from being a drug target for metabolism, a tension METRNL now shares.
GLP-1 agonists. Not exerkines, but the practical comparator for any candidate metabolic hormone. The semaglutide research overview and 5-Amino-1MQ profile cover the pathways METRNL research is usually positioned against.
Sourcing METRNL for research
Peptides.SO does not list METRNL. None of the 119 suppliers tracked on the platform (10,922 priced listings as of 25 September 2026) carries it, because it is a recombinant protein outside the synthetic-peptide catalogue. Researchers source it from recombinant-protein vendors (the R&D Systems, PeproTech, Sino Biological and Abcam catalogues all carry human and mouse METRNL) and should check three things: the expression system (mammalian HEK293 material is glycosylated; E. coli material is not), endotoxin specification for any immune-cell work, and the bioactivity assay used to qualify each lot. For the vocabulary of protein specifications, the glossary and the COA interpretation guide are the relevant references on this site.
Frequently asked questions
Is METRNL a peptide?
No. It is a 311-residue glycosylated protein. "Meteorin-like peptide" is a misnomer that appears on some supplier sites; the product is a recombinant protein.
What does it do in mice?
Raising circulating Metrnl increases energy expenditure and improves glucose tolerance through eosinophil-dependent IL-4 release and alternative macrophage activation in fat (PMID 24906147). Adipocyte Metrnl also protects against diet-induced insulin resistance through PPARγ without changing body weight (PMID 26307585).
What is its receptor?
KIT, the stem cell factor receptor tyrosine kinase, at least on endothelial cells (PMID 35709278). Whether the adipose and immune effects use the same receptor is not settled.
Is it a diabetes biomarker?
Not a validated one. The most recent meta-analysis found lower circulating levels in type 2 diabetes with confidence and prediction intervals too wide for clinical use (PMID 40956671).
Is it anti-inflammatory?
In adipose tissue and in the 2014 model, yes. The 2026 review documents pro-inflammatory roles in other settings and a possible negative effect on anti-tumour immunity (PMID 41365208).
Can I buy it from a peptide supplier?
Not from any supplier on this platform. It is a recombinant-protein product from life-science reagent companies.
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This article is for educational and research purposes only. METRNL is a recombinant research protein for in-vitro and preclinical use and is not intended for human or animal administration. Nothing on this page is medical advice.