Agouti-Related Peptide (AgRP)
Evidence: CNeuroendocrine / Appetite-Energy Balance Signaling
Evidence Snapshot
What this grade covers
B for human cDNA identity and in vitro MC3R/MC4R receptor pharmacology (Ollmann 1997). C for direct human plasma/circulating observational evidence (Katsuki 2001; fasting/hunger study; Vehapoglu 2016 pediatric) -- these measure full-length/general circulating AGRP, not a specific fragment. D for AgRP(83-132) fragment-specific feeding activity, which is RAT-ONLY (Rossi 1998, intracerebroventricular) -- no human fragment administration exists. Overall page grade: C.
Regulatory Context
Native AgRP is an endogenous human neuropeptide and is not itself an FDA-approved drug product. No AgRP-based drug candidate has reached FDA-regulated human clinical trials identified in this review.
In Plain English
A quick, research-focused overview. It does not replace, and cannot outrank, the detailed evidence below.
What is it?
A hypothalamic neuropeptide that antagonizes the MC3R and MC4R melanocortin receptors, opposing alpha-MSH signaling in the pathway that regulates appetite and energy balance.
Why are researchers interested in it?
Studied for its role in the melanocortin appetite-regulation circuit and its relationship to obesity, fasting, and alpha-MSH.
What does the evidence look like?
Direct human evidence is observational (blood measurement) only; no administration study of native AgRP or its active fragment exists in humans. Fragment-specific (AgRP 83-132) activity evidence is rat-only.
Biggest things to know
Circulating AgRP is higher in people with obesity and correlates with plasma alpha-MSH. A 48-hour fast raised AgRP more in lean than obese men, but this change was dissociated from subjective hunger ratings.
What don't we know yet?
Whether administering AgRP or its active fragment to humans would have any effect -- no such study exists.
Research Takeaway
Native human AgRP was identified via cDNA cloning and acts as a selective antagonist at the MC3R and MC4R melanocortin receptors in vitro.
Evidence boundary: Not evidence of any in-human administered effect; mouse in vivo phenotype is animal-scoped.
See all 4 evidence claims →Quick Summary
Agouti-related peptide (AgRP) is a hypothalamic neuropeptide that blocks melanocortin-4 receptor signaling, the same receptor pathway alpha-MSH activates. Circulating AgRP is observed to be higher in people with obesity, though it has never been administered to humans in a research study.
Mechanism & Research Overview
Agouti-related peptide (AgRP) is a hypothalamic neuropeptide that blocks melanocortin-4 receptor signaling, the same receptor pathway alpha-MSH activates. Circulating AgRP is observed to be higher in people with obesity, though it has never been administered to humans in a research study.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Native human AgRP was identified via cDNA cloning and acts as a selective antagonist at the MC3R and MC4R melanocortin receptors in vitro.
Does not establish
Evidence boundary: Not evidence of any in-human administered effect; mouse in vivo phenotype is animal-scoped.
Sources: Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein
Supported
Circulating plasma AgRP is higher in obese men than nonobese men and correlates with visceral fat, fasting insulin, leptin, and plasma alpha-MSH.
Does not establish
Evidence boundary: Association only; not causal; general circulating AGRP, not fragment-specific.
Sources: Plasma levels of agouti-related protein are increased in obese men
Supported
A 48-hour fast raises plasma AgRP more in lean men than in obese men; postprandial AgRP changes were dissociated from subjective hunger/satiety ratings in this study.
Does not establish
Evidence boundary: Must NOT be presented as "AgRP tracks hunger" -- the source found the opposite (dissociation).
Sources: Regulation of plasma agouti-related protein and its relationship with hunger in lean and obese men
Supported
A C-terminal AgRP fragment, AgRP(83-132), increased food intake and antagonized alpha-MSH's effect when given intracerebroventricularly to rats.
Does not establish
Evidence boundary: Must never be described as human evidence or as evidence for full-length human AgRP's own activity; must not be merged with the human circulating-AGRP claims above.
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
No study has administered native AgRP or its active fragment to humans; all human evidence is observational (blood measurement) only.Safety Consideration
The only fragment-specific (AgRP(83-132)) activity evidence is rat-only; human circulating-AGRP studies measure general/full-length AGRP and must not be conflated with fragment-specific activity.
Research Areas Being Studied
Research areas discussed on this page reflect the Neuroendocrine / Appetite-Energy Balance Signaling category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Alpha-Melanocyte-Stimulating Hormone and Agouti-Related Protein: Do They Play a Role in Appetite Regulation in Childhood Obesity? (2016):
- Regulation of plasma agouti-related protein and its relationship with hunger in lean and obese men (2016):
- Plasma levels of agouti-related protein are increased in obese men (2001):
- Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein (1997):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Alpha-Melanocyte-Stimulating Hormone and Agouti-Related Protein: Do They Play a Role in Appetite Regulation in Childhood Obesity? | 2016 | Underweight, healthy, and obese children | Direct plasma measurement of both alpha-MSH and AgRP in a pediatric cohort spanning underweight, healthy-weight, and obese children, assessing associations with anthropometric/nutritional markers. | ||
| Regulation of plasma agouti-related protein and its relationship with hunger in lean and obese men | 2016 | Lean men (n=10) and obese men (n=7), 48-hour fast | A 48-hour fast raised plasma AgRP more in lean than obese men, with a decrease in leptin; postprandial AgRP reduction (2-4h after a meal) was dissociated from subjective hunger and satiety ratings. | ||
| Plasma levels of agouti-related protein are increased in obese men | 2001 | 15 obese men, 15 nonobese men | Plasma AGRP significantly higher in obese men than nonobese men (p<0.01); correlated with visceral fat area, total fat area, fasting insulin, glucose infusion rate, serum leptin, and plasma alpha-MSH, independent of total fat area. | ||
| Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein | 1997 | Human AGRP cDNA; in vitro receptor assay; transgenic mouse phenotype | Human AGRP cDNA identified; recombinant AgRP is a potent, selective antagonist of MC3R and MC4R melanocortin receptors in vitro. Ubiquitous expression of human AGRP in transgenic mice caused obesity without altering pigmentation. |
Animal / Cell / Preclinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| A C-Terminal Fragment of Agouti-Related Protein Increases Feeding and Antagonizes the Effect of Alpha-Melanocyte Stimulating Hormone in Vivo | 1998 | Rats, intracerebroventricular (ICV) administration | AgRP(83-132), a C-terminal fragment of AgRP, given ICV to rats (1 nmol) increased 24h food intake (32.9+/-2.3g vs 23.0+/-1.4g saline, p<0.05) and antagonized the effect of alpha-MSH. |
Regulatory Documents & Official Trial Registries
No Regulatory Documents & Official Trial Registries Listed Yet
This section will be updated as sources are added.
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Human evidence for AgRP is observational only -- it has never been administered to people in a research study.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-08-28.
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