Vaspin: a novel serpin with insulin-sensitizing effects

Abstract

Background: A variety of substances, including free fatty acids, leptin, tumor necrosis factor-α, acylation-stimulating protein, adiponectin, and resistin, are secreted by adipocytes. They modulate insulin sensitivity and are new therapeutic targets in metabolic syndrome. Objective: To identify novel adipokines derived from visceral adipose tissues. Method: We used the PCR-based cDNA subtraction method to screen the genes predominantly expressed in visceral white adipose tissues (WATs) in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of abdominal obesity and type 2 diabetes. Results/conclusions: We identified the vaspin gene (Serpina12) which is upregulated in visceral WATs of OLETF rats. Vaspin mRNA was barely detectable at 6 weeks of age and it was abundantly and exclusively expressed in visceral WATs at 30 weeks of age, when OLETF rats reach their peak body weight. However, vaspin mRNA decreased with worsening of diabetes and body weight loss. Vaspin mRNA increased with treatment of thiazolidinediones (pioglitazone). Administration of recombinant vaspin into high-fat high-sucrose chow-induced obese ICR mice improved glucose tolerance and insulin sensitivity. Vaspin may be the compensatory molecule in the pathogenesis of metabolic syndrome and vaspin recombinant protein or vaspin-mimicking agents such as vaspin analogs, antibodies or small molecule agents may be the link to drug discovery and development.

Keywords::

• insulin resistance
• metabolic syndrome
• obesity
• serine protease
• serpin

Acknowledgements

This work was supported by the Japan Heart Foundation/Pfizer Grant for Research on Hypertension, Hyperlipidemia and Vascular Metabolism, Yamanouchi Foundation for Research on Metabolic Disorders, Grant-in-Aid for Scientific Research (C), Ministry of Education, Science and Culture, Japan (14571025, 17590829) to J Wada.

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