Adropin
A liver- and brain-secreted peptide that tells the body whether to burn carbohydrate or fat and keeps the vascular endothelium healthy; low levels track with insulin resistance and cardiovascular disease in humans.
Also known as ENHO gene product, energy homeostasis associated protein, adropin 34-76
Observational — Human data without randomisation. Suggestive, and easily confounded.
Consistent rodent mechanistic work since the 2008 discovery paper, and a substantial human cross-sectional literature linking low adropin to metabolic and cardiovascular disease. No interventional human data whatsoever.
How it works
Adropin is encoded by ENHO and expressed in liver and brain, with expression regulated by feeding state and by dietary macronutrient composition. Its best-characterised metabolic action is suppression of pyruvate dehydrogenase kinase 4, which releases the brake on pyruvate dehydrogenase and pushes skeletal muscle toward glucose oxidation rather than fatty acid oxidation — the opposite of what most 'fat-burning' compounds do, and the reason it improves glucose disposal. In endothelium it upregulates eNOS through VEGFR2-PI3K-Akt signalling, improving flow-mediated dilation. GPR19 has been proposed as its receptor, though this remains contested. Human data are entirely correlational: low serum adropin associates with obesity, type 2 diabetes, NAFLD, coronary artery disease and, in some cohorts, cognitive decline.
Targets: GPR19, Pyruvate dehydrogenase kinase 4, eNOS/nitric oxide pathway, VEGFR2-Akt signalling
Dosing
| Protocol | Dose | Frequency | Route |
|---|---|---|---|
| No human protocol existsNot applicable. | — | not established | subcutaneous |
- · Animal studies use body-weight-scaled intraperitoneal dosing over one to two weeks. There is no human dose, no human PK and no clinical trial. Adropin is far more useful right now as a biomarker than as an injectable.
Cycling
Not applicable.
Pharmacology
- Half-life
- Not established in humans. Rodent work suggests rapid clearance requiring repeated or infusion dosing.
- Onset
- Metabolic effects in rodents appear over days to weeks of repeated administration; endothelial effects are faster.
- Routes
- subcutaneous, intravenous
- Molecule
- Endogenous secreted peptide (ENHO gene product, 43-residue mature form)
- Sequence length
- 43 amino acids
Handling
- Diluent
- Bacteriostatic water
- Lyophilised
- Freezer at -20 C.
- Reconstituted
- Refrigerated, short term only.
Mixing
Available only as a research reagent in microgram quantities.
Side effects
- commonUnknown in humans— No administration study has ever been run in people.
Do not use if
- Human use outside research — there is no safety dataset of any kind.
What to monitor
- · Serum adropin can be measured by ELISA and is a legitimate research biomarker, but reference ranges vary widely between assays.
Legal status
Research reagent. Not approved or marketed as a therapeutic anywhere.
References
- Kumar et al. 2008, Cell Metabolism — identification of adropin as a secreted factor regulating metabolic homeostasis (preclinical)
- Gao et al. 2015, Molecular Metabolism — adropin regulates fuel selection via PDK4 (preclinical)
Mechanism in depth
Encoded by the ENHO gene and regulated by feeding state, adropin appears to act on GPR19 and to improve insulin sensitivity and endothelial function in rodents. It is unusual in being membrane-associated as well as secreted, which complicates interpreting circulating measurements.
What usually goes wrong
The receptor assignment itself is disputed, so mechanistic claims built on GPR19 are less solid than they read. As with irisin, human data is observational - adropin correlates with metabolic health - and no intervention has tested direction of causation.
Receptor targets
- GPR19 — Proposed; the receptor assignment is not universally accepted
Improved insulin sensitivity and endothelial nitric oxide signalling in animal models
Genuinely uncertain
- The GPR19 receptor assignment is contested in the literature.
- No human interventional trial exists.
- Assay reliability for circulating adropin has the same class of problems that undermined the early irisin literature.