Nesfatin-1
The satiety peptide found in the rat hypothalamus in 2006, what animal work shows, and why human blood studies disagree
Nesfatin-1 is the front end of a larger protein, nucleobindin-2. In 2006 researchers showed that injecting it into rat brains reduced eating, and that blocking it made rats eat more. It is made in the brain, in the same stomach cells that make ghrelin, and in fat tissue. In people it has only ever been measured in blood: levels have been reported higher, lower and unchanged in obesity, diabetes and polycystic ovary syndrome, depending on the study. No one has given nesfatin-1 to a person, its receptor is still unknown, and there is no human dose.
No established human dose Details ↓
Recommended Dosing
No established human dose
Nesfatin-1 has never been given to a person in the sources read. Every human study here measures it, in blood or in stomach tissue, in people with obesity, diabetes, eating disorders or after surgery, and reviews describe its effects on eating and weight from animal work, where it was injected into the brain or bloodstream.
What is it?
Nesfatin-1 was found by looking for proteins in the hypothalamus that change with feeding. The precursor, nucleobindin-2 (NUCB2), is a calcium-binding protein of 396 amino acids; nesfatin-1 is its first 82 amino acids after the signal sequence, and the 2006 discovery paper found it in rat cerebrospinal fluid. Injected into the brain's ventricles, it reduced food intake in a dose-dependent way, and given every day it lowered body weight. An antibody that neutralised it made rats eat more, and suppressing the NUCB2 gene made them gain weight. The effect did not need leptin signalling, since it worked in rats with a broken leptin receptor, and it appeared to run through the brain's melanocortin system.
Later rodent work filled in where and how. Injected into the lateral parabrachial nucleus, a brainstem relay for feeding signals, nesfatin-1 shrank meal size, excited glucose-sensing neurons and raised a heat-producing protein in brown fat, effects that a melanocortin blocker weakened. Two animal studies found that labelled nesfatin-1 injected into a vein crosses the blood-brain barrier, slowly and without a saturable transporter, and reaches brain tissue mostly intact, which matters because much of the body's nesfatin-1 is made outside the brain. A 2021 systematic review concluded that its receptor has still not been identified, although the signalling it triggers looks like a G protein-coupled receptor of the Gi type.
Outside the brain, nesfatin-1 is made in the stomach, in the very endocrine cells that make the hunger hormone ghrelin: in stomach tissue from people having sleeve gastrectomy, about four in five nesfatin-1 cells also contained ghrelin. It is also made and released by fat tissue, more from fat under the skin than from fat around the organs, and in mice its production rose on a high-fat diet and fell during fasting. That gives it a plausible role as a signal from both gut and fat to the brain.
In people the evidence is entirely measurement, and the measurements disagree. A study using a newly built assay found that fasting nesfatin-1 fell as body weight and body fat rose in lean young men. Obese adults in an acupuncture trial had lower levels than lean controls, and levels rose with weight loss; adults with metabolic syndrome also had lower levels. But obese Chinese children had higher levels than lean children, and a study across five weight bands found no clear relationship. In anorexia nervosa it was lower in one small study, and within a larger group it tracked anxiety rather than body weight. Meta-analyses mirror this: no overall difference in type 2 diabetes in one, a significant one in another, no difference in polycystic ovary syndrome in one and a higher level in another, with extreme heterogeneity throughout.
Part of the problem is technical. Many commercial kits detect the whole precursor and nesfatin-1 together, which is why so many papers write NUCB2/nesfatin-1, and different kits give different numbers. Blood levels also shift with diet, drugs and surgery: they fell after both gastric bypass and sleeve gastrectomy in people with diabetes. Until assays are standardised and the receptor is known, nesfatin-1 is an interesting appetite signal in rodents and an uncertain marker in people. It has never been tested as a treatment.
Mechanism of Action
Nesfatin-1 is cut from a larger protein in the brain, stomach and fat; in rodents it acts on brain feeding centres through the melanocortin system, but its own receptor has not been found.
Satiety in the brain
Injected into the brain of rats it reduces meal size and body weight, independently of leptin and through melanocortin signalling (PMIDs 17036007, 28484396).
Crossing into the brain
In mice, nesfatin-1 from the blood crosses the blood-brain barrier slowly by a non-saturable route, so gut and fat sources could signal the brain (PMIDs 18006117, 17950952).
Gut and fat sources
It is made in stomach endocrine cells alongside ghrelin and in fat tissue, where diet and fasting change its output (PMIDs 23515787, 20427481).
Unknown receptor
No receptor has been identified; signalling studies suggest a Gi-coupled G protein receptor (PMID 34566899).
Published Research
These are studies of nesfatin-1 read from their PubMed abstracts: the 2006 discovery, rodent studies of where it acts and how it reaches the brain, human tissue studies, human blood measurements in obesity, metabolic disease, eating disorders and after bariatric surgery, six meta-analyses and three reviews. Nesfatin-1 was given only to animals; in people it was measured.
Discovery: a satiety molecule in the rat hypothalamus
Nesfatin-1, cut from NUCB2, was found in rat cerebrospinal fluid and fell in the paraventricular nucleus during starvation. Injected into the brain's ventricles it cut food intake in proportion to dose, and given chronically it lowered body weight; a neutralising antibody raised appetite, and gene knockdown led to weight gain. It worked in leptin-receptor-mutant rats, and blocking melanocortin signalling abolished it.
Acting in a brainstem feeding relay
Microinjected into the lateral parabrachial nucleus of rats, nesfatin-1 reduced night-time food intake by shrinking meals rather than reducing their number, excited glucose-inhibited neurons, and over ten days slowed weight gain and raised UCP1 in brown fat. A melanocortin receptor blocker weakened these effects.
It enters the mouse brain intact
Radiolabelled nesfatin-1 injected into a vein in mice entered the brain at a modest rate that excess unlabelled peptide did not slow, so transport was not saturable. Most of it arrived intact, about two-thirds crossed fully into brain tissue, and it left the brain again by bulk flow.
Stable in blood, cleared from the brain in about 24 minutes
After intravenous injection, nesfatin-1 stayed stable in blood for at least 20 minutes and crossed the blood-brain barrier by a non-saturable route, with 0.3% in brain tissue at 10 minutes. Injected into the ventricles, it disappeared with a half-time of 23.8 minutes, no faster than albumin, suggesting it leaves with the normal turnover of spinal fluid.
Made and released by fat tissue
In human and mouse fat depots, NUCB2 messenger RNA, nesfatin-1 protein and its secretion were highest in fat under the skin. Mice on a high-fat diet had more of the protein and fasting mice less, and insulin, dexamethasone and inflammatory cytokines raised its production in tissue explants.
Made in the same stomach cells as ghrelin
In stomach tissue from obese patients having sleeve gastrectomy, nesfatin-1 appeared in endocrine cells, 78% of which also held ghrelin. Patients with a BMI of 55 to 65 had more nesfatin-1 cells and fewer ghrelin cells than patients with a BMI of 40 to 50.
Lower in heavier men, with a new assay
Using a newly built sandwich ELISA for human nesfatin-1, the discovery group measured 43 lean young men and found fasting levels fell as BMI, body fat and blood glucose rose; nine men with high BMI were also measured, and subgroups had glucose and meal tests.
Lower in obesity, rising with weight loss
Sixty-four obese adults without diabetes had lower plasma nesfatin-1 than 58 lean controls, and levels fell as BMI and waist size rose. After 45 days of diet with or without acupuncture, weight fell by 7.0% and 4.3% and nesfatin-1 rose in both groups, more with acupuncture.
Lower in metabolic syndrome
In a case-control study of 84 adults in Saudi Arabia, serum nesfatin-1 was lower in the 44 with metabolic syndrome than in 40 controls and fell as weight, waist circumference and BMI rose.
Higher in obese children
Among 156 Chinese children, serum nesfatin-1 and copeptin were both higher in the 101 with obesity and in those with insulin resistance than in lean children, and the two peptides rose together.
No clear link to body weight across five bands
Measured across five BMI groups from underweight to severely obese, serum nesfatin-1 rose slightly, though not significantly, up to the overweight band and then fell in the obese bands, which the authors read as no clear relationship with BMI.
Lower in restricting anorexia nervosa
Seven women with restricting-type anorexia nervosa had lower plasma nesfatin-1 than eight healthy women of the same age (about 6.2 against 8.9 ng/ml), while their acyl and des-acyl ghrelin were higher.
In anorexia, it tracked anxiety, not weight
In 64 women in hospital with anorexia nervosa, NUCB2/nesfatin-1 did not correlate with BMI, but patients with high anxiety scores had about 65% higher levels than those with low anxiety, and levels correlated with the anxiety scale.
Falls after bariatric surgery
In people with type 2 diabetes, fasting plasma nesfatin-1 fell significantly in the year after gastric bypass (12 patients) and sleeve gastrectomy (6 patients), and the fall tracked the drop in fasting glucose. Obestatin was measured too and rose after sleeve gastrectomy only.
Type 2 diabetes: no overall difference
Pooling seven studies with 328 patients and 294 controls, this meta-analysis found no overall difference in circulating nesfatin-1 in type 2 diabetes. Newly diagnosed patients had higher levels and treated patients lower ones.
Type 2 diabetes: a link, with very high heterogeneity
Eight case-control and cross-sectional studies with 305 patients and 205 controls showed a significant relationship between serum nesfatin-1 and type 2 diabetes, but heterogeneity was extreme (I-squared 98%), which limits what the pooled result means.
Polycystic ovary syndrome: no difference
This meta-analysis found no significant difference in blood nesfatin-1 between women with polycystic ovary syndrome and controls, overall or when split by ethnicity, sample type or obesity.
Polycystic ovary syndrome: higher, especially with higher BMI
Pooling 14 studies, this meta-analysis found higher nesfatin-1 in polycystic ovary syndrome than in controls, with the clearest difference in studies where mean BMI was over 25, the opposite conclusion to another meta-analysis published months earlier.
Higher in depression, in Asian studies
Nine studies with 567 patients and 447 controls, mostly from Asia, showed higher plasma nesfatin-1 in depression, with very high heterogeneity that subgroup analysis could not explain and no sign of publication bias.
What 500 papers say about eating and metabolism
This review covers the evidence, almost all from animals, that nesfatin-1 and NUCB2 reduce food intake and body weight and influence glucose and fat metabolism, and sets out the gaps that remain.
Its receptor is still unknown
A systematic review of 70 studies found that the receptor for nesfatin-1, the 82-amino-acid fragment of 396-residue NUCB2, has not been identified, although its signalling increasingly points to a Gi protein-coupled receptor.
Heart and blood pressure effects
This review gathers mainly experimental evidence that nesfatin-1, besides suppressing appetite, controls water intake and glucose balance and acts on central and peripheral control of the heart and blood vessels.
No Established Human Dose
Nesfatin-1 has never been given to a person in the sources read. Every human study here measures it, in blood or in stomach tissue, in people with obesity, diabetes, eating disorders or after surgery, and reviews describe its effects on eating and weight from animal work, where it was injected into the brain or bloodstream. There is no human pharmacology, no tolerability data and no amount that could be stated for people.
What this rests on: PMID 17036007, PMID 20550530, PMID 32229144.
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 Nesfatin-1 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 Nesfatin-1 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 Nesfatin-1, 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 Nesfatin-1 stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Nesfatin-1. 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 Nesfatin-1 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; effects on eating and weight come from rodents (PMIDs 17036007, 32229144); In rats, chronic injection into the brain lowered body weight and raised brown-fat heat production, effects that in people would not be harmless (PMIDs 17036007, 28484396). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Nesfatin-1. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Nesfatin-1 has not been given to people, so no human side effects have been reported”).
Interactions
Unknown: a PubMed search for human interaction studies of Nesfatin-1 (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 Nesfatin-1 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 Nesfatin-1's expected mass, 9,551.9 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
Nesfatin-1 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
Nesfatin-1 is a research peptide and blood marker; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is nesfatin-1?
An 82-amino-acid fragment of the protein nucleobindin-2, found in 2006 to reduce eating when injected into rat brains. It is made in the brain, stomach and fat tissue.
?Has nesfatin-1 been tested in people?
Only measured. No study in the sources read has given it to a person; human studies compare its blood levels across conditions.
?Is nesfatin-1 high or low in obesity?
Both have been reported. Several adult studies found it lower in obesity and metabolic syndrome, a study of children found it higher, and another found no clear relationship. Assays differ, which may explain some of this.
?Does nesfatin-1 work like ghrelin?
In the opposite direction. Ghrelin stimulates appetite, while nesfatin-1 suppressed it in rats, yet the two are made in the same stomach cells.
?What receptor does nesfatin-1 use?
It is not known. A 2021 systematic review found the evidence points toward a Gi-coupled G protein receptor but no receptor has been identified.
?Is there a nesfatin-1 dose?
No. It has never been given to people, so there is no human dose of any kind.
References
- [pubmed] Oh-I S, et al. "Identification of nesfatin-1 as a satiety molecule in the hypothalamus." Nature, 2006;443(7112):709-12. PMID: 17036007.
- [pubmed] Yuan JH, et al. "Nesfatin-1 in the Lateral Parabrachial Nucleus Inhibits Food Intake, Modulates Excitability of Glucosensing Neurons, and Enhances UCP1 Expression in Brown Adipose Tissue." Front Physiol, 2017;8:235. PMID: 28484396.
- [pubmed] Price TO, et al. "Permeability of the blood-brain barrier to a novel satiety molecule nesfatin-1." Peptides, 2007;28(12):2372-81. PMID: 18006117.
- [pubmed] Pan W, et al. "Nesfatin-1 crosses the blood-brain barrier without saturation." Peptides, 2007;28(11):2223-8. PMID: 17950952.
- [pubmed] Ramanjaneya M, et al. "Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity." Endocrinology, 2010;151(7):3169-80. PMID: 20427481.
- [pubmed] Stengel A, et al. "Ghrelin and NUCB2/nesfatin-1 are expressed in the same gastric cell and differentially correlated with body mass index in obese subjects." Histochem Cell Biol, 2013;139(6):909-18. PMID: 23515787.
- [pubmed] Tsuchiya T, et al. "Fasting concentrations of nesfatin-1 are negatively correlated with body mass index in non-obese males." Clin Endocrinol (Oxf), 2010;73(4):484-90. PMID: 20550530.
- [clinical-trial] Guo Y, et al. "Plasma nesfatin-1 level in obese patients after acupuncture: a randomised controlled trial." Acupunct Med, 2014;32(4):313-7. PMID: 24813558.
- [pubmed] Alotibi MN, et al. "Serum nesfatin-1 and galanin concentrations in the adult with metabolic syndrome. Relationships to insulin resistance and obesity." Saudi Med J, 2019;40(1):19-25. PMID: 30617376.
- [pubmed] Yin C, et al. "Copeptin and Nesfatin-1 Are Interrelated Biomarkers with Roles in the Pathogenesis of Insulin Resistance in Chinese Children with Obesity." Ann Nutr Metab, 2020;76(4):223-232. PMID: 33027789.
- [pubmed] Ozkan Y, et al. "Acylated and desacylated ghrelin, preptin, leptin, and nesfatin-1 Peptide changes related to the body mass index." Int J Endocrinol, 2013;2013:236085. PMID: 24371438.
- [pubmed] Ogiso K, et al. "Plasma nesfatin-1 concentrations in restricting-type anorexia nervosa." Peptides, 2011;32(1):150-3. PMID: 20937336.
- [pubmed] Hofmann T, et al. "NUCB2/nesfatin-1 Is Associated with Elevated Levels of Anxiety in Anorexia Nervosa." PLoS One, 2015;10(7):e0132058. PMID: 26162003.
- [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.
- [review] Zhai T, et al. "Circulating Nesfatin-1 Levels and Type 2 Diabetes: A Systematic Review and Meta-Analysis." J Diabetes Res, 2017;2017:7687098. PMID: 29445751.
- [review] Reyes-Lucía E, et al. "A meta-analysis about the relationship of serum nesfatin-1 levels in patients with type 2 diabetes mellitus." Biomedica, 2025;45(3):436-445. PMID: 40865110.
- [review] Wang M, et al. "Blood nesfatin-1 levels in patients with polycystic ovary syndrome: a systematic review and meta-analysis." Front Endocrinol (Lausanne), 2023;14:1275753. PMID: 38327900.
- [review] Venkata Nagaraju K, et al. "Nucleobindin-2 derived nesfatin-1 in polycystic ovary syndrome: a PRISMA and GRADE-compliant systematic review and meta-analysis with diagnostic test accuracy." Minerva Endocrinol (Torino), 2024;49(1):111-121. PMID: 37943280.
- [review] Liu M, et al. "Plasma levels of nesfatin-1 as a new biomarker in depression in Asians: evidence from meta-analysis." Biomarkers, 2020;25(3):228-234. PMID: 32116029.
- [review] Schalla MA, et al. "NUCB2/nesfatin-1 - Inhibitory effects on food intake, body weight and metabolism." Peptides, 2020;128:170308. PMID: 32229144.
- [review] Rupp SK, et al. "Nesfatin-1 Receptor: Distribution, Signaling and Increasing Evidence for a G Protein-Coupled Receptor - A Systematic Review." Front Endocrinol (Lausanne), 2021;12:740174. PMID: 34566899.
- [review] Angelone T, et al. "Nesfatin-1 in cardiovascular orchestration: From bench to bedside." Pharmacol Res, 2020;156:104766. PMID: 32201244.
- [other] UniProt P80303 (NUCB2_HUMAN), chain residues 25-106, nesfatin-1; read October 28, 2026. https://www.uniprot.org/uniprotkb/P80303/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.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.