Adropin
Also known as: ENHO peptide, energy homeostasis-associated protein, ADR
Endogenous peptide hormone / hepatokine
What it is
Adropin is a naturally produced peptide hormone researched for its roles in metabolic health, heart function, and blood vessel protection. Athletes, biohackers, and metabolic health enthusiasts have taken interest in it for its potential to improve insulin sensitivity, support cardiac efficiency, and protect against oxidative stress.
The scientific side
adropin is a 76-amino-acid peptide encoded by the ENHO gene, produced primarily in the liver and brain. It operates through a tissue-specific network of signaling pathways rather than a single universal receptor-cascade. In endothelial cells, adropin activates VEGFR2-dependent Akt/ERK/eNOS signaling, increasing endothelial nitric oxide synthase (eNOS) expression and nitric oxide availability, which underpins its vascular-protective actions. In skeletal muscle, adropin enhances insulin-stimulated Akt phosphorylation and promotes translocation of the glucose transporter GLUT4 to the cell surface, thereby improving glucose uptake and reducing insulin resistance. In the liver, PP2A/AMPK signaling provides mechanistic support for adropin's suppression of hepatic glucose production. In neural tissue, NB-3/Notch signaling is the best-supported pathway, with adropin also activating Akt/CREB/BDNF cascades in the hippocampus to enhance spatial memory. A putative receptor, GPR19, has been proposed but remains disputed. In cardiac tissue, adropin reduces hexosamine biosynthesis pathway activity, lowering O-GlcNAcylation of the fatty acid oxidation enzyme LCAD, which increases LCAD activity and reduces accumulation of long-chain acylcarnitines—a mechanism relevant to heart failure with preserved ejection fraction. Additionally, adropin activates the Nrf2/HO-1 antioxidant response pathway, upregulating protective enzymes (HO-1, NQO-1, GPX1) and reducing reactive oxygen species and pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β. Circulating adropin concentrations are consistently reduced in type 2 diabetes, coronary artery disease, and sepsis-induced cardiomyopathy, suggesting it tracks broader cardiometabolic stress. Skeletal muscle AMPK activation by adropin is not universal, and direct adipose AMPK activation remains unproven based on current evidence. Cross-tissue evidence also indicates that adropin modulates granulosa cell signaling through AKT and ERK1/2 pathways and influences oocyte maturation in reproductive tissue, and that ENHO gene expression is upregulated in liver, brain, and white adipose tissue under chronic stress conditions, linking adropin to broader stress-responsive energy regulation.
Class: Endogenous peptide hormone / hepatokine
Administration & storage
- Administration
- Intraperitoneal (mouse models — HFpEF studies)Intracerebroventricular (rat cognition model)Intravenous or systemic route implied in SAH mouse model (exact route not specified in abstract)
- Storage
- No human storage protocols established. Peptide hormone; standard cold-chain storage (2–8°C for short-term, −20°C for long-term) would be consistent with similar recombinant peptides, but no adropin-specific guidance is reported in the reviewed abstracts.
Legal & regulatory status
Not approved as a drug. No IND or NDA on record for human therapeutic use. Research compound only.
Not currently listed on the WADA Prohibited List. No specific adropin prohibition identified in available literature.
Not approved for human therapeutic use. No Health Canada drug identification number assigned.
What it's studied for
- Heart failure with preserved ejection fraction (HFpEF) Preclinical — animal models only
- Endothelial dysfunction and cardiovascular risk in type 2 diabetes Observational human studies
- Neuroprotection after subarachnoid hemorrhage (SAH) Preclinical — animal model
- Insulin resistance and glucose metabolism Preclinical and observational human data
- Sepsis-induced cardiomyopathy (SIMD) protection Preclinical — cellular and mouse models
- Blood pressure variability in older adults Observational — prospective cohort
- Cardiometabolic biomarker in coronary artery disease Observational human studies
- Cognitive function and spatial memory Preclinical — rat model
- Gestational diabetes mellitus (GDM) — biomarker role Meta-analysis of observational studies
Safety signals
- Elevated adropin associated with increased blood pressure variability — potential adverse cardiovascular implication of supraphysiologic levels
- Adropin modulates granulosa cell viability via AKT signaling and increases apoptosis markers in porcine ovarian cells in vitro
- Adropin reduces granulosa cell proliferation and suppresses estradiol secretion via PKA/ERK1/2 signaling in porcine follicles
- No targeted therapies or dose-safety data established for human use; transition from bench to bedside requires rigorous dose optimization and long-term safety trials
- Potential interaction with antihypertensive therapy — association between adropin and BP variability was strongest in participants already on antihypertensive medications
- ENHO knockout mice showed exacerbated HFpEF pathology including diastolic dysfunction, hypertrophy, and fibrosis — suggesting adropin deficiency itself is harmful but supraphysiologic dosing safety is unknown
- GPR19 receptor identity disputed — unclear off-target receptor binding profile for exogenous adropin
- Paradoxically elevated adropin observed in gestational diabetes mellitus — direction of adropin changes may be context- and state-dependent, complicating therapeutic targeting
No peer-reviewed studies indexed for this peptide yet.
Frequently asked
Is adropin approved for human use?
No. As of the research reviewed, adropin is not approved by the FDA, Health Canada, or any reviewed regulatory authority for human therapeutic use. It is a research compound studied in animal models and through observational human studies only. No human clinical trials testing therapeutic adropin administration were identified.
What is adropin supposed to do for metabolic health?
Based on preclinical and observational research, adropin is associated with improved insulin sensitivity, reduced hepatic glucose production, better fatty acid utilization in the heart, and lower levels of pro-inflammatory cytokines. Lower circulating adropin has been observed in people with type 2 diabetes and coronary artery disease. However, these are associations from animal models and observational studies — no human interventional trials have confirmed therapeutic benefit from administered adropin.
Has adropin been studied in heart failure?
Yes, in preclinical animal models. Two independent mouse studies showed recombinant adropin reversed features of heart failure with preserved ejection fraction (HFpEF), including cardiac fibrosis and diastolic dysfunction, via Nrf2/HO-1 antioxidant pathways and metabolic enzyme regulation. These findings are promising but have not yet been translated to human clinical trials.
Does adropin help with cognition or brain health?
Animal data suggest it may. Rat studies found intracerebroventricular adropin improved spatial memory via Akt/CREB/BDNF pathways in the hippocampus, and mouse SAH models showed neuroprotective effects post-brain hemorrhage. No human cognitive trials involving adropin administration have been reported in the reviewed literature.
What are the risks of taking adropin?
Human safety data for administered adropin do not exist in the reviewed literature. Preclinical signals include potential effects on reproductive hormones and ovarian cell viability, an association between higher adropin and blood pressure variability in older adults on antihypertensives, and an unresolved receptor binding profile. The absence of human dosing data means risks cannot be quantified, and use outside of supervised research settings cannot be evaluated for safety.