Vaspin.com

Named in 2005, from the fat of an obese rat

Vaspin is short for visceral adipose tissue-derived serine protease inhibitor. Hida and colleagues reported it in PNAS in 2005 after cloning it from the visceral fat of a rat model of abdominal obesity and type 2 diabetes.1 In the rat, expression rose with obesity and insulin levels and fell as diabetes worsened; given to obese mice, the protein improved glucose tolerance and insulin sensitivity, and the authors named it an insulin-sensitising adipocytokine.1

SERPINA12: gene, protein, structure

The human gene is SERPINA12, serpin family A member 12, at 14q32.13, with eight exons.2 The HGNC approved the symbol in 2004 and lists vaspin and OL-64 as aliases.3 UniProt entry Q8IW75 records a 414-residue precursor of about 47 kDa, a reactive centre loop at residues 364 to 382, and N-linked glycans at three asparagines that slightly lower heparin affinity without changing inhibitory activity or thermal stability.4 Five X-ray structures are in the Protein Data Bank.4 Mutagenesis showed that the P1′ glutamate (Glu379) limits the inhibition rate, that Arg302 on beta-sheet C is needed for recognition by kallikrein 7, and that vaspin is a remarkably thermostable serpin.5

Where vaspin is made

Human fat expresses it patchily: in paired samples from 196 people, vaspin mRNA was detectable in only 23% of visceral and 15% of subcutaneous samples, never in lean subjects, and more often in type 2 diabetes.6 Keratinocytes are the main source in skin, where psoriatic lesions express less than uninvolved skin.7 It has been found in mouse hypothalamus and human cerebrospinal fluid, the gene is expressed in human gastric mucosa, and serum levels vary through the day with food intake.8

Kallikrein 7, kallikrein 14 and GRP78

In 2013 Heiker and colleagues identified human kallikrein 7 (KLK7) as the first protease inhibited by vaspin, by the classical serpin mechanism, in which the cleaved reactive centre loop traps the protease in a stable complex.9 They found vaspin–KLK7 complexes in human plasma, showed that KLK7 cleaves human insulin, and found that the glucose-tolerance gain in treated mice depended entirely on serpin activity, supporting the hypothesis that vaspin protects circulating insulin from degradation.9 In 2018 kallikrein 14 was reported as a second target, with distinct exosites and opposite effects of heparin on the two reactions.10

Separately, vaspin binds cell-surface GRP78, a chaperone that reaches the plasma membrane under ER stress: vaspin-transgenic mice were protected from diet-induced obesity, glucose intolerance and fatty liver, vaspin-deficient mice developed glucose intolerance, and recombinant vaspin raised Akt and AMPK phosphorylation in liver cells, an effect blocked by anti-GRP78 antibodies.11 Injected vaspin also reduced food intake in mice, with glucose lowering that lasted at least six days.8 These are animal and cell findings.

Human studies, and where they disagree

A serum ELISA was described in 2008. In 187 people, vaspin was higher in women than men, did not differ between normal glucose tolerance and type 2 diabetes, correlated with BMI and insulin sensitivity in the normal-tolerance group, and rose after four weeks of physical training.12 Pooled estimates: vaspin was 0.52 ng/mL higher in obesity (six studies, 1,826 participants) and 0.36 ng/mL higher in type 2 diabetes (eleven studies, 1,570 patients), with large variation between studies.13 It was not significantly different in metabolic-associated fatty liver disease (13 studies, SMD 0.46, interval spanning zero), where BMI was flagged as a confounder,14 but higher in gestational diabetes (22 studies, SMD 0.72).15 A 2025 review sees growing evidence of a positive cardiovascular role, yet notes significant disparities between animal and in-vitro studies and human studies, and a lack of standardised methods that gives inconsistent and sometimes contradictory results.16

Who works on vaspin

The literature is the buyer map for Vaspin.com:

• Metabolic-disease biotech working on the serpin–kallikrein axis or the GRP78 pathway.
• Diagnostics groups running adipokine ELISA panels in obesity, diabetes and pregnancy cohorts.
• Reagent suppliers: recombinant vaspin, antibodies, ELISA kits and kallikrein substrates.
• Dermatology and skin-biology groups.
• Obstetric and reproductive endocrinology teams.
• A review site, course or society resource, since the domain is the search term.

Vaspin, SERPINA12, serpin A12, OL-64

UniProt’s recommended name is serpin A12, the gene is SERPINA12, and OL-64 is an older alias in all three databases.234 Vaspin.com holds the six-letter common name.

1. Hida K et al. Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity.PNAS, 2005
2. SERPINA12 serpin family A member 12 [Homo sapiens], Gene ID 145264.NCBI Gene
3. SERPINA12, HGNC:18359.HGNC
4. Q8IW75, SPA12_HUMAN: Serpin A12.UniProt
5. Ulbricht D et al. A unique serpin P1′ glutamate and a conserved beta-sheet C arginine are key residues for activity, protease recognition and stability of serpinA12 (vaspin).Biochem J, 2015
6. Klöting N et al. Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes.Biochem Biophys Res Commun, 2006
7. Saalbach A et al. Vaspin: a link of obesity and psoriasis?Exp Dermatol, 2012
8. Klöting N et al. Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects.Diabetologia, 2011
9. Heiker JT et al. Vaspin inhibits kallikrein 7 by serpin mechanism.Cell Mol Life Sci, 2013
10. Ulbricht D et al. Kallikrein-related peptidase 14 is the second KLK protease targeted by the serpin vaspin.Biol Chem, 2018
11. Nakatsuka A et al. Vaspin is an adipokine ameliorating ER stress in obesity as a ligand for cell-surface GRP78/MTJ-1 complex.Diabetes, 2012
12. Youn BS et al. Serum vaspin concentrations in human obesity and type 2 diabetes.Diabetes, 2008
13. Feng R et al. Higher vaspin levels in subjects with obesity and type 2 diabetes mellitus: a meta-analysis.Diabetes Res Clin Pract, 2014
14. Zhu Y et al. Association of circulating vaspin levels and patients with metabolic-associated fatty liver disease: a systematic review and meta-analysis.Lipids Health Dis, 2022
15. Zhou B et al. Serum vaspin levels in gestational diabetes mellitus: a meta-analysis.Metab Syndr Relat Disord, 2023
16. Dabrowski KM, Bieganski HM, Rozanska-Waledziak A. From adipose tissue to endothelial cells: pleiotropic role of vaspin in pathogenesis of metabolic and cardiovascular diseases.Biomedicines, 2025