Nesfatin-1

NUCB2-derived peptide, nucleobindin-2 fragment (residues 1–82), nesfatin-1(1-82); the active core is often studied as nesfatin-1(30-59)

Metabolic & weight

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Summary

Class: Naturally occurring 82-amino-acid peptide, cleaved from the N-terminal end of the protein nucleobindin-2 (NUCB2). Research material is a synthetic or recombinant copy
Mechanism: Acts in the hypothalamus and brainstem to suppress food intake independently of leptin, raises blood pressure and sympathetic tone, improves glucose handling in rodents, and increases anxiety-like behaviour — through a receptor that has still not been definitively identified
Routes studied: Intracerebroventricular, intraperitoneal, intravenous and subcutaneous (rodents). No human administration published. Community: essentially none
Dose range reported: Rodents: picomole-to-nanomole central doses; peripheral 10–100 µg/kg ranges in some studies. No human dose exists at any level. Community-reported: no reliable reports
Half-life: Not well characterised; peripheral nesfatin-1 appears to act within 30–60 minutes in rodents and crosses the blood–brain barrier to some extent. Serum stability data are limited
Storage: Lyophilised: freeze or refrigerate, protect from light. Reconstituted: refrigerate and use promptly; an 82-residue peptide is prone to aggregation and adsorption
Regulatory status: Not approved anywhere; a research reagent, not a drug candidate at present

Doses are as reported in studies or by the community — never recommendations.

1What it is

Nesfatin-1 was discovered in 2006 by a Japanese group looking for new molecules in the appetite centres of the rat brain (Oh-I 2006, Nature). It is a fragment of nucleobindin-2, a protein previously known for binding calcium and DNA, and it got its name — "NEFA/NUCB2-encoded satiety and fat-influencing protein" — from the finding that injecting it into the brain made rats eat less, while blocking it made them eat more. It is produced in the hypothalamus (paraventricular, supraoptic and arcuate nuclei), the brainstem, and, surprisingly, in the same stomach cells that make ghrelin, as well as in pancreas, fat and heart.

Twenty years on it remains a physiology story rather than a therapy. Its receptor is still unidentified (a G-protein-coupled receptor is assumed from signalling studies), there are no human administration trials, and interest has shifted toward measuring circulating levels as a marker in obesity, diabetes, eating disorders and mood disorders. It appears in peptide-community discussion mostly because of its "satiety peptide" label, and as a curiosity next to the GLP-1 drugs. Anyone describing a protocol with it is working from rodent data alone.

2How it's thought to work

Appetite suppression. Central nesfatin-1 reduces food intake in a leptin-independent way (it works in leptin-resistant and leptin-receptor-deficient animals), acting partly through melanocortin, oxytocin and CRH neurons and reducing the drive to eat during the dark (active) phase. Peripheral injection also reduces intake in mice, implying it crosses into the brain (Shimizu 2009).

Cardiovascular. Central nesfatin-1 raises blood pressure via melanocortin and sympathetic pathways (Yosten & Samson 2009); peripheral effects on heart and vessels are reported in both directions depending on model.

Glucose. Peripheral nesfatin-1 lowered blood glucose in hyperglycaemic db/db mice in an insulin-dependent way (Su 2010) and is reported to enhance insulin secretion and sensitivity in several rodent studies.

Anxiety and stress. Central administration increases anxiety- and fear-related behaviours in rats (Merali 2008) and nesfatin-1 neurons respond to stress; it is co-expressed with CRH.

Gastric and other. Slows gastric emptying, affects reproductive hormones in some models, and has been studied in cardioprotection and bone.

Nesfatin-1, cleaved from the larger precursor NUCB2, acting in the hypothalamus and brainstem to reduce food intake. It works independently of leptin, which is why it remains of interest where leptin signalling is already impaired.Schematic — not to scale

3What the research shows

Food intake and body weight in rodents

Reduced feeding after central injection (Oh-I 2006) and after peripheral injection in mice (Shimizu 2009); chronic central infusion reduced weight gain. Effect size is modest and some labs find weaker peripheral effects than others. [1][2]

Blood pressure and cardiovascular effects

Central nesfatin-1 produces sustained rises in mean arterial pressure in conscious rats (Yosten & Samson 2009). Protective effects in cardiac ischaemia–reperfusion models are also reported. Direction depends on site and dose. [4]

Glucose regulation

Anti-hyperglycaemic effects in diabetic mice (Su 2010); insulinotropic effects on islets . No human data beyond association. [5]

Anxiety, mood, sleep

Anxiogenic in rats (Merali 2008); some antidepressant-like findings in other paradigms; reports of reduced REM sleep. Conflicting. [6]

Graded B (observational only; not an effect of giving the peptide)

Human associations

Many case–control studies measure circulating nesfatin-1 in obesity, type 2 diabetes, anorexia nervosa, depression and polycystic ovary syndrome, with inconsistent directions — partly because assays cross-react with full-length NUCB2 (Stengel & Taché, reviews). These tell us about physiology and assay problems; they say nothing about what injecting it does.

Not gradednone

Human administration

No published trial in which nesfatin-1 was given to people.

4Reported side effects and interactions

Literature-reported

No human safety data of any kind. In rodents, the most consistent "side effect" is the one that matters: raised blood pressure. Anxiogenic behaviour is the second.

Community-reported

too few credible reports to summarise. Treat anything online as untested.

Theoretical. a peptide that raises sympathetic tone and blood pressure and increases anxiety-like behaviour in animals is a poor fit for anyone with hypertension, cardiovascular disease or an anxiety disorder; its hypoglycaemic effect in diabetic mice suggests caution with glucose-lowering medicines; its reproductive-axis effects in rodents are unresolved. An 82-residue peptide is also large enough to be immunogenic with repeated injection — an ordinary concern for any peptide of this size with no human data.

Interactions. none studied. Mechanistic overlap with melanocortin, oxytocin and CRH pathways.

Markers researchers commonly monitor

No compound-specific human markers are established. Given the rodent pharmacology, if this were ever in a protocol:

Marker	Why it's watched
Blood pressure and heart rate	the clearest rodent signal is a pressor effect.
Fasting glucose and insulin	the compound lowers glucose in diabetic mice; relevant both as an effect and as a hypoglycaemia risk alongside other agents.
Anxiety scale (e.g. GAD-7)	anxiogenic in rats.
Weight and appetite log	the headline effect, if any, would show here.
CBC and CMP	general baseline; no human safety data exist.
Serum nesfatin-1/NUCB2 assays are research tools with cross-reactivity problems and are not useful for monitoring exogenous dosing

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Rarely encountered outside laboratories, and expensive per milligram because of its length. Supplied , often in sub-milligram vials. gently with sterile water or buffer; large peptides adsorb to plastic and aggregate on shaking, so swirl, use low-binding tubes if possible, and avoid repeated freeze–thaw. There is no community dosing convention to calibrate against, which is itself a warning.

Open in calculator, pre-loaded →

6Commonly studied alongside

In the literature: ghrelin (co-localised in the stomach, opposite effects on appetite), leptin, oxytocin, CRH and the melanocortin system. In community discussion it is mentioned next to Semaglutide (#3) and other GLP-1 agonists, and to AOD-9604 and MOTS-c in "metabolic" lists, without any combined or even single-agent human data.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; research reagent only; not a compounding substance
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport (WADA)	Not specifically listed; as a non-approved substance it falls under S0 †

8Open questions

What is the receptor? Without it, drug development has stalled.
Does peripheral nesfatin-1 reliably reduce food intake, and in which species?
Any human pharmacokinetic or safety data — none exist.
Whether circulating levels mean anything given assay cross-reactivity with full-length NUCB2.

9References

1Oh-I S et al. (2006). Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. PubMed · DOI
2Shimizu H et al. (2009). Peripheral administration of nesfatin-1 reduces food intake in mice: the leptin-independent mechanism. Endocrinology. PubMed · DOI
3Stengel A et al. (2009). Identification and characterization of nesfatin-1 immunoreactivity in endocrine cell types of the rat gastric oxyntic mucosa. Endocrinology. PubMed · DOI
4Yosten GLC, Samson WK (2009). Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am J Physiol Regul Integr Comp Physiol. PubMed · DOI
5Su Y et al. (2010). The novel function of nesfatin-1: anti-hyperglycemia. Biochem Biophys Res Commun. PubMed · DOI
6Merali Z et al. (2008). Nesfatin-1 increases anxiety- and fear-related behaviors in the rat. Psychopharmacology. PubMed · DOI
7Stengel A, Taché Y (2013). Role of NUCB2/nesfatin-1 in the hypothalamic control of energy homeostasis. Horm Metab Res [verify journal]. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

26 Oct 2026Profile published — awaiting medical review

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