Spexin
A 14-amino-acid galanin-family peptide that is dramatically suppressed in obesity and, when given back to animals, reduces food intake and improves lipid handling.
Also known as NPQ, neuropeptide Q, SPX, C12orf39 product
Animal data only — Rodent or other animal studies. Dose translation to humans is genuinely uncertain.
Solid rodent and fish pharmacology plus strong human correlational data showing spexin falls in obesity and rises after weight loss. No human administration studies at all.
How it works
Spexin was discovered by bioinformatics rather than bioassay — a hidden-Markov-model search for unannotated peptide hormones flagged the C12orf39 gene product. It signals through GALR2 and GALR3 but not GALR1, which matters because GALR1 mediates the orexigenic effects of galanin; spexin therefore behaves as galanin's functional opposite for feeding. In rodents it reduces food intake, delays gastric emptying, decreases long-chain fatty acid uptake by adipocytes and improves glucose tolerance. Human adipose tissue spexin mRNA is the single most downregulated transcript in obesity in some datasets, and circulating levels rise after bariatric surgery. Roles in nociception, reproduction and salt-water balance have also been described, which makes it less clean as a metabolic drug candidate than it first appears.
Targets: GALR2, GALR3, Adipocyte fatty acid uptake
Dosing
| Protocol | Dose | Frequency | Route |
|---|---|---|---|
| No human protocol existsNot applicable. | — | not established | subcutaneous |
- · Rodent studies use body-weight-scaled daily intraperitoneal dosing, often for two weeks. No human dose has been established and the peptide's short half-life means any naive injectable protocol would be pharmacologically pointless.
Cycling
Not applicable.
Pharmacology
- Half-life
- Very short — a small unmodified linear peptide with no half-life extension. Not characterised in humans.
- Onset
- Acute anorectic effects within an hour in rodents; metabolic changes over weeks of repeated dosing.
- Routes
- subcutaneous, intravenous
- Molecule
- Endogenous 14-amino-acid amidated neuropeptide (galanin family)
- Sequence length
- 14 amino acids
Handling
- Diluent
- Bacteriostatic water
- Lyophilised
- Freezer at -20 C.
- Reconstituted
- Refrigerated, days only.
Mixing
Research-grade only. The C-terminal amidation matters for activity; non-amidated material is inactive.
Side effects
- commonUnknown in humans— Never administered to people in a published study.
- commonDelayed gastric emptying— Demonstrated in rodents; would plausibly translate as nausea or fullness in humans.
Do not use if
- Human use outside research.
Combining it
- redundantsemaglutide — Both slow gastric emptying and reduce intake; there is no reason to expect additive benefit and good reason to expect additive GI misery.
What to monitor
- · Serum spexin is a research biomarker only.
Legal status
Research reagent. Not approved anywhere.
References
- Mirabeau et al. 2007, Genome Research — bioinformatic identification of spexin (preclinical)
- Walewski et al. 2014, Obesity — spexin is downregulated in human obesity and reduces food intake in rodents (preclinical)
Mechanism in depth
A 14-residue peptide encoded by the C12orf39 gene, acting as a ligand at galanin receptors 2 and 3 but not galanin receptor 1 - a selectivity that matters, because GALR1 signalling drives the appetite-stimulating effects of galanin while GALR2/3 signalling appears to do the opposite. Circulating levels are reported to be lower in obesity.
What usually goes wrong
The human evidence is associative - spexin is lower in people with obesity - and association is being sold as mechanism. Lower spexin in obesity is as consistent with consequence as with cause, and no interventional human trial has tested whether raising it changes anything.
Receptor targets
- Galanin receptor 2 and 3 — Selective over GALR1
Reduced food intake and altered lipid handling in animal models
Genuinely uncertain
- No human interventional data exists.
- Whether low spexin in obesity is causal or consequent is untested.
- No validated human dose exists by any route.