Obestatin
Evidence: EGastrointestinal / Gut-Hormone Signaling
Evidence Snapshot
What this grade covers
Applies to native Obestatin's proposed anorexigenic/metabolic efficacy claims specifically. This grade reflects: (1) a complete absence of controlled human administration evidence of any kind (a dedicated, multi-angle search of PubMed, general web search, and ClinicalTrials.gov found none); (2) a majority-negative rodent replication record for the original anorexigenic claim (Nogueiras 2007, Zizzari 2007 partial-only, Gourcerol 2007 review); (3) one positive rodent replication (Lagaud 2007) that was formally RETRACTED by its own journal in 2009; and (4) direct, independent contradiction of the original proposed receptor mechanism (GPR39) by two separate research groups (Lauwers 2006, Holst 2007), with the receptor question still explicitly unresolved rather than settled in obestatin's favor.
Regulatory Context
Obestatin is not an FDA-approved drug product, and no Obestatin-based drug candidate has reached FDA-regulated human clinical trials identified in this review. No related-programme regulatory evidence exists for this subject.
Research Takeaway
Obestatin is a 23-amino-acid peptide co-derived, along with Ghrelin, from the same preproghrelin precursor gene, but is a separate, distinct mature peptide product with its own independent evidence base.
Evidence boundary: Identity/precursor-biology statement; does not itself establish any efficacy or receptor mechanism. Do not use Ghrelin evidence to support this page, and do not state Obestatin is 'the opposite of Ghrelin' as an established fact.
See all 4 evidence claims →Quick Summary
Obestatin is a peptide co-derived from the same preproghrelin gene as ghrelin. A 2005 study proposed that it opposes ghrelin's appetite-stimulating effects through a receptor called GPR39, but independent research over the following years found this original finding difficult to replicate, directly contradicted the proposed GPR39 mechanism, and even saw a separate positive replication formally retracted. No controlled human administration study of obestatin has been identified in the published literature -- the available evidence is entirely preclinical (rodent) or observational/cell-based in nature.
Mechanism & Research Overview
Obestatin is a peptide co-derived from the same preproghrelin gene as ghrelin. A 2005 study proposed that it opposes ghrelin's appetite-stimulating effects through a receptor called GPR39, but independent research over the following years found this original finding difficult to replicate, directly contradicted the proposed GPR39 mechanism, and even saw a separate positive replication formally retracted. No controlled human administration study of obestatin has been identified in the published literature -- the available evidence is entirely preclinical (rodent) or observational/cell-based in nature.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Obestatin is a 23-amino-acid peptide co-derived, along with Ghrelin, from the same preproghrelin precursor gene, but is a separate, distinct mature peptide product with its own independent evidence base.
Does not establish
Evidence boundary: Identity/precursor-biology statement; does not itself establish any efficacy or receptor mechanism. Do not use Ghrelin evidence to support this page, and do not state Obestatin is 'the opposite of Ghrelin' as an established fact.
Sources: Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake
Supported
The original 2005 rodent study proposing that obestatin suppresses food intake and opposes ghrelin's effects, acting through the receptor GPR39, has not been consistently replicated by independent research groups, and the GPR39 receptor mechanism has been directly contradicted by two independent studies.
Does not establish
Evidence boundary: All evidence discussed here, both original and replication/contradiction, is RODENT or IN-VITRO -- no human data exists on either side of this question. Do not state GPR39 is confirmed as obestatin's receptor; do not state the original anorexigenic effect is established.
Sources: Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake; Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents; Obestatin Partially Affects Ghrelin Stimulation of Food Intake and Growth Hormone Secretion in Rodents; Obestatin Does Not Activate Orphan G Protein-Coupled Receptor GPR39; GPR39 Signaling Is Stimulated by Zinc Ions but Not by Obestatin
Supported
A 2007 rodent study that reported obestatin reduces food intake and suppresses body weight gain was formally retracted by its journal in 2009.
Does not establish
Evidence boundary: This is a documented retraction, included for scientific-transparency reasons; the original (now-withdrawn) findings must never be cited as supporting evidence for obestatin's effects. Never cite this paper's original findings as supporting evidence under any framing.
Sources: [RETRACTED] Obestatin Reduces Food Intake and Suppresses Body Weight Gain in Rodents
Supported
No controlled human administration study of obestatin (intravenous, subcutaneous, oral, or intranasal) was identified in a dedicated search of the published literature and clinical trial registries. All human-adjacent obestatin research located is observational (plasma-level correlation with disease states) or based on isolated human cells/tissue, not administration to a living human subject.
Does not establish
Evidence boundary: This claim is itself the boundary statement, based on the absence of evidence documented via a dedicated multi-angle search (PubMed, general web, ClinicalTrials.gov). Never state or imply obestatin has been shown to affect appetite, weight, or any other outcome in humans through direct administration -- no such study exists in the literature reviewed.
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
Independent rodent replication attempts of the original 2005 anorexigenic claim were largely negative (Nogueiras 2007) or only partial/conditional (Zizzari 2007, fed-state-only ghrelin-antagonism, no independent effect). A separate positive rodent replication (Lagaud 2007) was formally retracted by its journal in 2009.Safety Consideration
Two independent research groups (Lauwers 2006, Holst 2007) found no binding or functional activity of obestatin at GPR39, directly contradicting the original 2005 paper's proposed receptor mechanism. The receptor question remains unresolved, not settled in obestatin's favor.Safety Consideration
Obestatin is co-derived from the same preproghrelin gene as Ghrelin, but this shared origin does not transfer Ghrelin's own (independently much stronger) human evidence base to Obestatin, and the two must never be presented as interchangeable.Safety Consideration
A dedicated, multi-angle search (PubMed, general web search, ClinicalTrials.gov API) found zero controlled human obestatin-administration studies of any kind. This is a fundamental evidence gap, not merely a limitation.
Research Areas Being Studied
Research areas discussed on this page reflect the Gastrointestinal / Gut-Hormone Signaling category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
No Human Study Findings Listed Yet
See preclinical, regulatory, and review sources below.
Study Tables by Evidence Type
Human Studies & Clinical Data
No Human Studies & Clinical Data Listed Yet
This section will be updated as sources are added.
Animal / Cell / Preclinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| [RETRACTED] Obestatin Reduces Food Intake and Suppresses Body Weight Gain in Rodents | 2007 | RETRACTED PAPER. This paper originally reported a positive anorexigenic/body-weight-suppressing effect of obestatin in rodents but was formally RETRACTED by the journal (Biochem Biophys Res Commun) on 2009-10-23 (retraction notice PMID 19777640). Included ONLY to document the retraction as negative/credibility context for the field's replication history. | RETRACTED -- must NEVER be cited as a positive source for obestatin's anorexigenic effect under any circumstance. Title explicitly marked [RETRACTED] to prevent misuse. | ||
| Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents | 2007 | rodent, not human | No effect of obestatin on food intake, body weight, body composition, energy expenditure, locomotor activity, respiratory quotient, or hypothalamic energy-balance neuropeptides; no effect on GH secretion in vivo; could not detect GPR39 mRNA in rat hypothalamus. | Comprehensive negative replication of the original 2005 anorexigenic claim. | |
| GPR39 Signaling Is Stimulated by Zinc Ions but Not by Obestatin | 2007 | Zinc ions, not obestatin, are a genuine GPR39 agonist -- a second, independent research group's direct contradiction of the original GPR39-obestatin receptor claim. | |||
| Obestatin Partially Affects Ghrelin Stimulation of Food Intake and Growth Hormone Secretion in Rodents | 2007 | rodent (mice), not human | Obestatin alone had no effect on food intake; it partially antagonized ghrelin's orexigenic effect, but only in fed mice (not fasted); obestatin alone had no direct GH effect but partially blocked ghrelin-stimulated GH release in vivo (not replicated ex vivo in pituitary explants). | No independent anorexigenic effect; in-vivo/ex-vivo discordance. | |
| Obestatin Does Not Activate Orphan G Protein-Coupled Receptor GPR39 | 2006 | I125-obestatin does not bind GPR39 and no functional effect of obestatin on GPR39-transfected cells was observed across three different radioiodinated obestatin forms and two GPR39-expressing cell types -- directly contradicts the original 2005 GPR39 claim. | |||
| Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake | 2005 | rat, not human | Original description of obestatin: rat administration suppressed food intake, inhibited jejunal contraction, and decreased body-weight gain; proposed GPR39 as the obestatin receptor. This original anorexigenic/GPR39 claim was directly contradicted by multiple independent later studies (see Obestatin page). | Rodent-only, never independently replicated in humans. Must not be cited as human efficacy evidence for either Ghrelin or Obestatin. On the Ghrelin page this is identity/precursor-context only (obestatin is a separate peptide co-derived from the same gene, not a Ghrelin form); on the Obestatin page it is the original primary source, superseded by the replication record. |
Regulatory Documents & Official Trial Registries
No Regulatory Documents & Official Trial Registries Listed Yet
This section will be updated as sources are added.
Review Articles / Secondary Sources
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Comment on 'Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake' | 2007 | Formal published scientific comment directly challenging the original 2005 Science paper's central claims. | |||
| Lack of Obestatin Effects on Food Intake: Should Obestatin Be Renamed Ghrelin-Associated Peptide (GAP)? | 2007 | Explicitly proposes renaming obestatin 'ghrelin-associated peptide (GAP)' given the consistent failure to replicate its proposed anorexigenic action. |
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
Educational information only. This page summarizes published preclinical and observational research on obestatin. There is no controlled human interventional evidence for this peptide, and this page does not constitute medical advice, a treatment recommendation, or dosing guidance of any kind.
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 2026-08-26.
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