Adropin: heart and metabolism hormone linked to energy balance (ENHO peptide)
A natural hormone made in the liver and brain that helps regulate blood sugar and supports blood vessel health; studied as a research tool in animals, not yet tested as a drug in humans.
- Class
- Endogenous peptide hormone (hepatokine / brain-derived)
- Status
- No approved therapeutic use; research molecule and cardiometabolic biomarker
- Best-supported effect
- Improved insulin sensitivity and endothelial function in rodent models; circulating levels correlate observationally with metabolic and cardiovascular disease risk in humans (biomarker association only, not therapeutic evidence)
- Main caveat
- No exogenous adropin has been administered in a completed human clinical trial; all human data is observational biomarker correlation; therapeutic effect in humans is not established
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
Snapshot
Class: Endogenous peptide hormone (hepatokine / brain-derived)
Evidence tier: Animal-only evidence
Status: No approved therapeutic use; research molecule and cardiometabolic biomarker
Best-supported effect: Improved insulin sensitivity and endothelial function in rodent models; circulating levels correlate observationally with metabolic and cardiovascular disease risk in humans (biomarker association only, not therapeutic evidence)
Main caveat: No exogenous adropin has been administered in a completed human clinical trial; all human data is observational biomarker correlation; therapeutic effect in humans is not established
What this is
Adropin is a 76-amino-acid secreted peptide hormone encoded by the ENHO (Energy Homeostasis Associated) gene, expressed primarily in liver and brain and detectable in serum, kidney, heart, pancreas, small intestine, and vascular endothelium. It was first identified in 2008 as a factor involved in energy homeostasis and macronutrient adaptation. Research has since expanded to include roles in glucose metabolism, insulin sensitivity, endothelial nitric oxide bioavailability, and neuroprotection in ischemia-reperfusion injury models. Adropin is an endogenous hormone, not an approved drug or validated therapeutic; its significance in the current literature is primarily as a biomarker and mechanistic research target. No clinical trial of exogenous adropin administration has been completed in humans.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | Observational biomarker only | Dozens of observational studies associate low circulating adropin with obesity, type 2 diabetes, NAFLD, and cardiovascular disease; no completed clinical trial of exogenous adropin administration identified |
| Animal | Moderate | Improved insulin sensitivity in diet-induced obese mouse models; endothelial eNOS upregulation; neuroprotection in rodent ischemia-reperfusion models; cardiac fuel metabolism effects |
| In vitro | Moderate | eNOS upregulation via VEGFR2–PI3K–Akt and VEGFR2–ERK1/2 pathways in endothelial cell studies; brain endothelial tight-junction tightening under ischemic conditions |
| Computational | None identified | No computational modeling or structure-prediction data attached |
| Mechanism | Plausible | eNOS and nitric oxide pathway well supported in cell and animal work; candidate receptor GPR19 proposed but not universally accepted; full receptor pharmacology incompletely characterized |
Human observational associations establish biomarker relevance only — they do not establish that administering exogenous adropin produces the same metabolic or cardiovascular effects seen with higher endogenous levels.
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Low circulating adropin associates with metabolic and cardiovascular disease risk | Supported (observational) | Human observational | High — many studies; causality direction not established |
| Improved insulin sensitivity and metabolic markers | Supported (animal) | Animal preclinical | Medium — rodent models; no human therapeutic trial |
| Endothelial function improvement via eNOS upregulation | Supported (in vitro / animal) | In vitro and animal | Medium — mechanism well characterized in cell and animal systems; not tested therapeutically in humans |
| Neuroprotection in ischemic injury | Supported (animal) | Animal preclinical | Low — rodent ischemia-reperfusion models only; no human data |
| Exogenous adropin as a therapeutic for metabolic or cardiovascular disease in humans | Not established | Human | High confidence in verdict — no completed human therapeutic trial identified; extrapolation from biomarker and preclinical data |
Notes on claim interpretation:
- Observational associations between endogenous adropin levels and disease markers support biomarker relevance only; they do not establish that exogenous adropin administration produces equivalent effects.
- "Supported (observational)" in row 1 reflects
verdict: supportedfor the biomarker correlation claim specifically; causality is not established.
Experimental exposure
This section reports exposure used in animal experiments. It does not establish human dosing.
| Context | System | Experimental exposure | Duration | Endpoint | Limitation |
|---|---|---|---|---|---|
| Metabolic / insulin-sensitivity studies | Diet-induced obese mice | Recombinant adropin (parenteral; exact dose not individually extracted in source) | Study-specific | Insulin sensitivity markers, diabetes-related metabolic parameters | Rodent model only; no human PK, safety, or dose-finding data |
| Endothelial function studies | Endothelial cell assays and animal vascular models | Recombinant adropin (concentration not individually extracted in source) | Study-specific | eNOS expression, nitric oxide bioavailability, vasodilation markers | In vitro and animal context; not translated to human exposure |
| Neuroprotection studies | Rodent ischemia-reperfusion injury models | Recombinant adropin (parenteral; exact dose not individually extracted in source) | Study-specific | Blood-brain barrier permeability, neurological outcome markers | Rodent ischemia model; no human translation established |
Exact dose values are not individually extracted in the available literature. No human pharmacokinetic or dosing context exists for exogenous adropin.
Preclinical safety signals
| Signal | System | Notes |
|---|---|---|
| No human safety data | — | No exogenous adropin has been administered in a completed human clinical or safety trial |
| Research-chemical adropin products | — | Source notes that research-chemical "adropin" products have no human pharmacokinetic, safety, or purity data |
| Unknown route and dose requirements | — | Appropriate route (likely parenteral given 76-aa size), dose, and pharmacokinetic profile for exogenous adropin in humans are entirely uncharacterized |
| Receptor biology incompletely characterized | — | GPR19 proposed as candidate receptor but not universally accepted; off-target effects are unknown |
Regulatory status
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | Not approved | No approved therapeutic indication; no registered clinical trial as a drug |
| EU (EMA) | Not approved | No approved indication identified in source |
| WADA | Not assessed in source | Source does not address anti-doping status; adropin is an endogenous peptide hormone |
| Research use | Research molecule | Used as recombinant peptide in preclinical animal studies only |
No approved therapeutic status identified. This card describes a research molecule and endogenous biomarker, not an approved medicine.
Mechanism
Adropin is encoded by the ENHO gene and expressed primarily in liver and brain, with detectable expression also in kidney, heart, pancreas, small intestine, and vascular endothelium. It is secreted and measurable in serum.
In endothelial cells, adropin upregulates endothelial nitric oxide synthase (eNOS) expression through the VEGFR2–PI3K–Akt and VEGFR2–ERK1/2 signaling pathways, increasing nitric oxide bioavailability and promoting vasodilation. In hepatocytes and skeletal muscle, adropin modulates fatty acid oxidation, glucose uptake, and insulin sensitivity; overexpression in diet-induced obese mouse models improved insulin sensitivity and reduced diabetes-associated markers. In the brain, adropin has been shown in rodent ischemia-reperfusion models to tighten endothelial tight junctions, reducing paracellular permeability of the blood-brain barrier under ischemic conditions.
A candidate receptor, GPR19, has been proposed, but this assignment is not universally accepted and the full receptor pharmacology of adropin remains incompletely characterized. Circulating adropin levels are regulated by nutritional state — rising with increased fat intake and falling during chronic energy excess — and are modulated by estrogen in humans.
The mechanistic data derive from cell assays and rodent models. Whether these pathways translate to equivalent effects from exogenous adropin administration in humans has not been established.
Chemistry
| Field | Value |
|---|---|
| Full name | Adropin (ENHO-encoded secreted peptide) |
| Gene | ENHO (Energy Homeostasis Associated) |
| Length | 76 amino acids |
| Topology | Linear |
| Primary expression | Liver, brain; also detectable in kidney, heart, pancreas, small intestine, vascular endothelium |
| Sequence | Not individually extracted in available literature |
| Molecular weight | Not individually extracted in available literature |
| Sequence confidence | Needs review — sequence not included in available literature |
Open questions
- Human therapeutic translation: No completed clinical trial of exogenous adropin administration in humans has been identified. Whether pharmacological elevation of adropin in humans replicates the metabolic and cardiovascular correlations seen with higher endogenous levels is the central unresolved question.
- Biomarker vs causal role: Observational associations between low adropin and disease are consistent, but causality direction is not established. Adropin may be a marker of metabolic state rather than a causal driver of disease outcomes.
- Receptor identity: GPR19 is proposed as the primary receptor but is not universally accepted. Confirming the receptor and downstream signaling specificity is necessary for targeted drug development.
- Pharmacokinetics and route: For a 76-amino-acid peptide, parenteral administration is likely required, but no human pharmacokinetic data (half-life, bioavailability, volume of distribution, clearance) are identified.
- Exogenous vs endogenous equivalence: Whether raising circulating adropin exogenously produces the same biological effects as higher endogenous levels — or produces distinct effects due to receptor occupancy, timing, or tissue distribution differences — is not established.
- Long-term safety: No preclinical chronic-exposure toxicology or human safety data are attached.
- Research-chemical product validity: Research-chemical adropin products circulate in peptide markets; their purity, accurate peptide identity, and pharmacological activity are unvalidated.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Which protein on cell surfaces does adropin actually bind to, and could that protein be a new drug target?
If the receptor were identified, it would immediately become a target for small-molecule drugs that mimic adropin, offering a pill-based alternative to peptide injections for heart and metabolic disease.
Does adropin keep a key blood vessel enzyme working properly under oxidative stress by stabilizing its protein partner, rather than just increasing how much of the enzyme is made?
If true, adropin-based drugs could preserve blood vessel health in diabetic and heart disease patients in situations where current nitric oxide therapies fail due to oxidative conditions, reducing risk of vascular complications.
Does the body cut adropin into two different versions that act differently in the liver and brain, explaining why it seems to do different things in different tissues?
If true, it would explain confusing findings in adropin research and tell drug developers whether to target the full hormone or just the shorter processed fragment, focusing development efforts more efficiently.
Do the two rigid proline pairs in adropin create fixed bends that are essential for its shape and activity, such that changing them would break the molecule?
If true, researchers could design short, rigid fragments of adropin that keep the critical shape while being small enough to develop as drugs, which would make adropin-based therapies far more practical and affordable.
Does adropin actively regulate hormone balance in the ovaries, so that low levels could cause the androgen excess that defines PCOS?
If true, restoring adropin levels could address the root hormonal imbalance in PCOS rather than just managing insulin resistance, offering a more targeted treatment for a condition affecting tens of millions of women.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.5326640009880066 | openfold3-mlx |
| ranking score | 0.7043740749359131 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.698 | global PDE — lower = better |
| disorder | 0.248 | fraction disordered |
| chain pair ipTM (A, B) | 0.533 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | — |
| hardware | — |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | — |
| diffusion samples | 1 |
| runtime | 134s |
| predicted by | mlx@peptide |
| predicted at | 2026-05-03 |
▸citationbibtex
@peptide{pep10960,
sequence = {STHPPQHGFDSANWSLFKEVHKFQPPKEYTQKLFETPFSDAVNQLIRNLEEDIEQLSYQAKLS},
target = {longevity},
author = {peptidemodel},
year = {2026},
status = {computed}
}