Obestatin
The ghrelin-gene peptide announced in 2005 as an appetite suppressor, the many labs that could not repeat it, and what measuring it in people shows
Obestatin is cut from the same precursor protein as ghrelin, the hunger hormone. Its 2005 discovery paper reported that it did the opposite of ghrelin in rats, suppressing food intake and weight gain, and that it worked through a receptor called GPR39. Within two years, several laboratories reported that it did not change eating in rats or mice and did not activate GPR39. Research has since moved to other possible roles, such as muscle repair in animals. In people it has only been measured in blood, where levels tend to be lower in obesity and higher in anorexia nervosa. It has never been given to a person.
No established human dose Details ↓
Recommended Dosing
No established human dose
Obestatin has never been given to a person in the sources read. The human studies here measure it in blood, in obesity, anorexia nervosa, after meals and after surgery, and the experiments that gave it were all in rats, mice or cells, where most failed to repeat the original effect on eating.
What is it?
The ghrelin gene makes one precursor protein, preproghrelin, which is cut into more than one peptide. In 2005 a team predicted from the sequence that a second hormone should sit further along the chain, isolated it from rat stomach and called it obestatin. In their experiments it did the reverse of ghrelin: it reduced food intake, slowed contraction of the jejunum and reduced weight gain in rats, and it bound an orphan receptor, GPR39. Two hormones with opposite effects from one gene made an elegant story, and the paper appeared in Science.
The story did not hold. Within three years, several independent groups injected obestatin into the bloodstream, abdomen or brain of rats and mice and found no change in food intake, gastric emptying, gastric motility, blood glucose, insulin or pituitary hormones. A seven-day continuous infusion at high doses did nothing to eating or weight. One group saw a brief drop in eating on the first day of brain infusion that vanished afterwards. Two groups found that obestatin did not activate GPR39 by any signalling route they tested, and that zinc did; GPR39 is now generally regarded as a zinc-sensing receptor. The original group published further work supporting GPR39 binding with a purified tracer, so the receptor question was argued rather than closed.
Since then, animal research has looked at other effects. Rats given obestatin healed acetic acid stomach ulcers faster, and in rats on a high-fat diet it lowered liver fat and insulin resistance. A 2026 review describes the most active current line: obestatin as a regulator of muscle formation, improving muscle regeneration after injury and strength in experimental models of steroid-induced wasting and Duchenne muscular dystrophy. A 2022 review concludes that obestatin and ghrelin oppose each other in some systems, work together in others, and give contradictory results in still others.
In people, obestatin has been measured but never given. The pattern is broadly consistent: levels are lower in obesity and higher in anorexia nervosa. A meta-analysis of nine studies found higher levels in normal-weight than in obese people, with very high heterogeneity, and a study of obesity and anorexia found obestatin fell as BMI, insulin resistance and leptin rose. In restricting anorexia nervosa, levels were higher than in controls and fell as patients ate more; women who are constitutionally thin but eat normally did not show the rise. Levels fell after seeing, smelling and chewing a meal, and after atropine, in lean but not obese volunteers, which suggests a link to the vagus nerve.
Surgery and disease shift it in less predictable ways. Obestatin did not change two years after gastric bypass in severely obese women, but rose after sleeve gastrectomy in people with diabetes. It was higher in children on haemodialysis, in younger children with Prader-Willi syndrome and in some neuroendocrine tumours, and it was linked to growing waist size in older women without predicting weight loss or poor appetite. None of these findings has made obestatin a diagnostic test, and nothing in the human literature supports taking it.
Mechanism of Action
Obestatin is a second peptide cut from the ghrelin precursor; its first reported effects on appetite and its receptor were disputed, and its role in the body is still uncertain.
Made with ghrelin
Cut from preproghrelin in the stomach, so ghrelin and obestatin come from one gene and are often measured as a ratio (PMIDs 16284174, 35454106).
Appetite claim not reproduced
Reduced eating in the discovery paper, but most rodent studies by other groups found no effect on eating, gastric emptying or weight (PMIDs 16284174, 18070755, 18508160).
Receptor in dispute
GPR39 was proposed as its receptor; other groups found zinc activates GPR39 and obestatin does not, while the original group reported binding with a purified tracer (PMIDs 17054911, 16959833, 18337590).
Tissue repair in animals
Animal work reports faster ulcer healing, less liver fat and better muscle regeneration (PMIDs 21804455, 29429367, 41784884).
Published Research
These are studies of obestatin read from their PubMed abstracts: the 2005 discovery, the rodent and receptor studies that tried to repeat it, later animal work, human blood measurements in obesity, anorexia nervosa, after meals and after bariatric surgery, a meta-analysis and two reviews. Obestatin was given only to animals or cells; in people it was measured.
Discovery: a second hormone from the ghrelin gene
Predicted from the proghrelin sequence and isolated from rat stomach, obestatin reduced food intake, inhibited jejunal contraction and lowered body-weight gain in rats, the opposite of ghrelin, and bound the orphan receptor GPR39.
No effect on eating when given into the brain
Injected into the brain's ventricles, obestatin did not change food intake in freely fed or food-restricted rats and did not blunt the extra eating that ghrelin causes.
No effect with or without CCK
Obestatin injected into the abdomen at up to 300 micrograms per kilogram did not change two-hour food intake in rats or mice or gastric emptying in rats, did not add to the satiety effect of CCK, and did not change stomach pressure or vagal nerve activity.
No effect in lean or obese rodents
Across a 30-fold range of abdominal doses in rats and diet-induced obese mice, and intravenous or intracisternal injection in anaesthetised rats, obestatin changed neither food intake, gastric emptying, fasting stomach motility nor blood glucose, while ghrelin given the same way did increase motility.
A week of high-dose infusion changed nothing
Continuous infusion of obestatin under the skin of rats, up to 1,000 nmol/kg a day for seven days, did not change food intake, body weight, weight loss during fasting, or glucose and insulin responses; it did not alter insulin release from islets or bind GLP-1 receptors.
A brief dip in eating that faded
A single brain injection in starved rats gave a trend toward eating less that was not significant. A 28-day brain infusion cut eating on the first day only, and body weight never differed from controls.
No effect on pituitary hormones
Intravenous or brain injection of obestatin in anaesthetised rats did not change growth hormone, prolactin, ACTH or TSH, and did not blunt the growth hormone rise caused by GHRH or the ghrelin-receptor agonist GHRP-2.
No effect even without ghrelin
To rule out ghrelin masking an effect, the authors tested ghrelin-knockout mice: obestatin did not change refeeding after a fast or gastric emptying in normal or knockout mice, and did not reverse ghrelin's speeding of gastric emptying.
It did not activate GPR39
Using a cAMP reporter like the original paper and a calcium flux method, the authors could not show any activation of GPR39 by obestatin; zinc at high concentrations did activate the receptor, and obestatin did not change that response.
Zinc, not obestatin, drives GPR39
Zinc stimulated several signalling pathways in GPR39-expressing cells while obestatin had no reproducible effect, no specific binding of three labelled forms of obestatin was found, GPR39 was absent from the hypothalamus and pituitary, and obestatin did not change acute food intake in mice.
The original group's case for GPR39
After abdominal injection in mice, obestatin switched on the early-response gene c-fos in stomach, intestine, fat, liver and kidney, where GPR39 was also found. With an HPLC-purified iodinated tracer, the authors reported binding to several tissues and to cells made to express GPR39, arguing that earlier negative results came from inactive tracers.
Faster healing of stomach ulcers in rats
Given twice a day into the abdomen for six days after acetic acid ulcers were induced, obestatin sped ulcer healing in rats, with changes in gastric blood flow, mucosal DNA synthesis and inflammatory cytokine expression.
Less liver fat in rats on a high-fat diet
Long-term obestatin injections in rats on a high-fat diet reduced liver enlargement, liver fat, blood lipids and insulin resistance, lowered food intake and weight gain, and raised adiponectin and the ratio of unacylated to acylated ghrelin.
Lower in obesity, higher in anorexia
In 10 obese people, 11 women with restricting anorexia nervosa and 11 controls, fasting obestatin was lower in obesity and higher in anorexia, and it fell as BMI, glucose, insulin, insulin resistance and leptin rose.
Meta-analysis: higher in normal weight than obesity
Nine studies with 566 people showed obestatin about 64 pg/mL higher in normal-weight than obese groups, with heterogeneity close to the maximum (I-squared 98.6%); total and active ghrelin were also higher in normal-weight groups.
Higher throughout a glucose test in anorexia
Ten women with restricting anorexia nervosa had higher obestatin, acyl ghrelin and des-acyl ghrelin than ten healthy women throughout an oral glucose tolerance test; all three fell after glucose in both groups, and the difference was largest for obestatin.
Falls as anorexia patients eat more
Obestatin was higher in patients with restricting anorexia nervosa than in controls, and it fell, along with des-acyl ghrelin, as their calorie intake increased during treatment.
Thin by constitution is different from anorexia
Over six samples across the day, obestatin was much higher in 15 women with anorexia nervosa than in controls, but not in 10 women who are constitutionally thin while eating normally; ghrelin-to-obestatin ratios were lower in anorexia.
Drops after sham feeding
Seeing, smelling and chewing a meal without swallowing raised ghrelin and lowered obestatin in eight women with anorexia nervosa and eight healthy women; both baseline levels and the changes were larger in anorexia.
Meals and atropine lower it in lean people only
In a randomised crossover study, breakfast and intravenous atropine each lowered plasma obestatin and the obestatin-to-ghrelin ratio in eight lean volunteers, with additive effects, but neither changed them significantly in eight obese volunteers.
Unchanged two years after gastric bypass
In 18 severely obese women who lost an average of 41.5 kg after Roux-en-Y gastric bypass, ghrelin and the ghrelin-to-obestatin ratio fell, while obestatin itself did not change.
Rises after sleeve gastrectomy, not bypass
In people with type 2 diabetes, fasting plasma obestatin rose in the year after sleeve gastrectomy (6 patients) but did not change after gastric bypass (12 patients), while nesfatin-1 fell after both.
No link to appetite or weight loss in older women
Among 110 women averaging 77 years followed for two years, obestatin was not related to weight change, malnutrition risk or poor appetite, but it correlated with an increase in waist circumference and was associated with metabolic syndrome.
Found in some neuroendocrine tumours
Obestatin was found in 19 of 152 neuroendocrine and related tumour samples, mainly of foregut origin, often in the same cells as ghrelin; its blood level during a standardised meal was measured in six healthy people and five patients with pancreatic tumours.
Ghrelin and obestatin: opposed, allied or contradictory
This review sorts the functions of the two sibling peptides into complex ones (eating, weight, gut motility, insulin secretion), complementary ones (beta cells, heart, muscle, nerve protection) and contradictory ones (white fat, heat production, sleep), and says obestatin's own roles remain less clear.
A new focus: muscle repair
After years of dispute over appetite and its receptor, this review describes obestatin as a regulator of muscle formation in experimental models, improving regeneration after acute injury and strength in steroid-induced muscle wasting and Duchenne muscular dystrophy.
No Established Human Dose
Obestatin has never been given to a person in the sources read. The human studies here measure it in blood, in obesity, anorexia nervosa, after meals and after surgery, and the experiments that gave it were all in rats, mice or cells, where most failed to repeat the original effect on eating. There is no human pharmacology or safety data and no amount that could be stated for people.
What this rests on: PMID 17919459, PMID 21139496, PMID 18508160.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Obestatin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Obestatin has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Obestatin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Obestatin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Obestatin. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Obestatin lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: No human administration study exists in the sources read; every dosing experiment was in animals or cells (PMIDs 16284174, 18508160); High-dose infusion for a week in rats changed neither eating, weight nor glucose handling (PMID 18508160). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Obestatin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Obestatin has not been given to people, so no human side effects have been reported”).
Interactions
Unknown: a PubMed search for human interaction studies of Obestatin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Obestatin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Obestatin's expected mass, 2,546.9 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine anywhere: no approval and no human treatment trial in the sources read). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Obestatin has not been given to people, so no human side effects have been reported.
Contraindications & Cautions
There is no product label and no human safety data.
Legal Status
Obestatin is a research peptide; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is obestatin?
A 23-amino-acid peptide cut from the same precursor protein as ghrelin, first described in 2005 as an appetite suppressor.
?Does obestatin suppress appetite?
The discovery paper said so, in rats. Six studies by five other groups found no effect on eating in rats or mice, and another saw only a one-day dip. In people its effect on appetite has never been tested.
?What is its receptor?
Disputed. The discovery paper named GPR39, but two groups found that GPR39 responds to zinc and not to obestatin; the original group later reported binding with a purified tracer.
?What do blood levels show?
Levels tend to be lower in obesity and higher in anorexia nervosa, falling as people with anorexia eat more. Results after bariatric surgery and in other diseases are mixed.
?Is obestatin used to build muscle?
Only in animal and cell studies, where it improved muscle regeneration in models of injury and muscle disease. It has not been tested for this in people.
?Is there an obestatin dose?
No. It has never been given to people, so there is no human dose of any kind.
References
- [pubmed] Zhang JV, et al. "Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake." Science, 2005;310(5750):996-9. PMID: 16284174.
- [pubmed] Seoane LM, et al. "Central obestatin administration does not modify either spontaneous or ghrelin-induced food intake in rats." J Endocrinol Invest, 2006;29(8):RC13-5. PMID: 17033253.
- [pubmed] Gourcerol G, et al. "Lack of interaction between peripheral injection of CCK and obestatin in the regulation of gastric satiety signaling in rodents." Peptides, 2006;27(11):2811-9. PMID: 16934368.
- [pubmed] Gourcerol G, et al. "Preproghrelin-derived peptide, obestatin, fails to influence food intake in lean or obese rodents." Obesity (Silver Spring), 2007;15(11):2643-52. PMID: 18070755.
- [pubmed] Unniappan S, et al. "Metabolic effects of chronic obestatin infusion in rats." Peptides, 2008;29(8):1354-61. PMID: 18508160.
- [pubmed] Sibilia V, et al. "Intracerebroventricular acute and chronic administration of obestatin minimally affect food intake but not weight gain in the rat." J Endocrinol Invest, 2006;29(11):RC31-4. PMID: 17259788.
- [pubmed] Yamamoto D, et al. "Neither intravenous nor intracerebroventricular administration of obestatin affects the secretion of GH, PRL, TSH and ACTH in rats." Regul Pept, 2007;138(2-3):141-4. PMID: 17055593.
- [pubmed] Depoortere I, et al. "Effect of peripheral obestatin on food intake and gastric emptying in ghrelin-knockout mice." Br J Pharmacol, 2008;153(7):1550-7. PMID: 18204478.
- [pubmed] Lauwers E, et al. "Obestatin does not activate orphan G protein-coupled receptor GPR39." Biochem Biophys Res Commun, 2006;351(1):21-5. PMID: 17054911.
- [pubmed] Holst B, et al. "GPR39 signaling is stimulated by zinc ions but not by obestatin." Endocrinology, 2007;148(1):13-20. PMID: 16959833.
- [pubmed] Zhang JV, et al. "Obestatin induction of early-response gene expression in gastrointestinal and adipose tissues and the mediatory role of G protein-coupled receptor, GPR39." Mol Endocrinol, 2008;22(6):1464-75. PMID: 18337590.
- [pubmed] Dembiński A, et al. "Administration of obestatin accelerates the healing of chronic gastric ulcers in rats." Med Sci Monit, 2011;17(8):BR196-200. PMID: 21804455.
- [pubmed] Khaleel EF, et al. "Obestatin protects and reverses nonalcoholic fatty liver disease and its associated insulin resistance in rats via inhibition of food intake, enhancing hepatic adiponectin signaling, and blocking ghrelin acylation." Arch Physiol Biochem, 2019;125(1):64-78. PMID: 29429367.
- [pubmed] Nakahara T, et al. "Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa." Biol Psychiatry, 2008;64(3):252-5. PMID: 17919459.
- [review] Zhang N, et al. "Meta-analysis of the relationship between obestatin and ghrelin levels and the ghrelin/obestatin ratio with respect to obesity." Am J Med Sci, 2011;341(1):48-55. PMID: 21139496.
- [pubmed] Harada T, et al. "Obestatin, acyl ghrelin, and des-acyl ghrelin responses to an oral glucose tolerance test in the restricting type of anorexia nervosa." Biol Psychiatry, 2008;63(2):245-7. PMID: 17706613.
- [pubmed] Uehara M, et al. "Increase in energy intake leads to a decrease in obestatin in restricting-type of anorexia nervosa." Exp Clin Endocrinol Diabetes, 2011;119(9):536-9. PMID: 21667437.
- [pubmed] Germain N, et al. "Ghrelin/obestatin ratio in two populations with low bodyweight: constitutional thinness and anorexia nervosa." Psychoneuroendocrinology, 2009;34(3):413-9. PMID: 18995969.
- [clinical-trial] Monteleone P, et al. "Deranged secretion of ghrelin and obestatin in the cephalic phase of vagal stimulation in women with anorexia nervosa." Biol Psychiatry, 2008;64(11):1005-8. PMID: 18474361.
- [clinical-trial] Maier C, et al. "Differential regulation of plasma obestatin and ghrelin by meal intake and the cholinergic system in lean, but not obese individuals." J Clin Endocrinol Metab, 2010;95(10):E214-8. PMID: 20660037.
- [pubmed] Roth CL, et al. "Ghrelin and obestatin levels in severely obese women before and after weight loss after Roux-en-Y gastric bypass surgery." Obes Surg, 2009;19(1):29-35. PMID: 18521699.
- [pubmed] Lee WJ, et al. "Differential influences of gastric bypass and sleeve gastrectomy on plasma nesfatin-1 and obestatin levels in patients with type 2 diabetes mellitus." Curr Pharm Des, 2013;19(32):5830-5. PMID: 23768444.
- [pubmed] Mora M, et al. "Obestatin does not modify weight and nutritional behaviour but is associated with metabolic syndrome in old women." Clin Endocrinol (Oxf), 2013;78(6):882-90. PMID: 22775400.
- [pubmed] Grönberg M, et al. "Ghrelin and obestatin in human neuroendocrine tumors: expression and effect on obestatin levels after food intake." Neuroendocrinology, 2013;97(4):291-9. PMID: 23147274.
- [review] Villarreal D, et al. "Diverse and Complementary Effects of Ghrelin and Obestatin." Biomolecules, 2022;12(4). PMID: 35454106.
- [review] Santos-Zas I, et al. "Obestatin: canonical and unexpected functions." Rev Endocr Metab Disord, 2026;27(2):317-330. PMID: 41784884.
- [other] UniProt Q9UBU3 (GHRL_HUMAN), peptide residues 76-98 with C-terminal leucine amide, obestatin; read October 28, 2026. https://www.uniprot.org/uniprotkb/Q9UBU3/entry
Sources & Citations
Every study on this page was read from its PubMed record on October 28, 2026. Status comes from Drugs@FDA (openFDA) and the EMA medicines list, read the same day. Grey Peptides sells nothing and links to no vendor.
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