SERPINA12 - serpin family A member 12 |Elisa - Clia - Antibody - Protein

Background

SERPINA12, also known as Vaspin (Visceral adipose tissue-derived serpin), is a member of the serpin (serine protease inhibitor) superfamily, which is widely recognized for its role in inhibiting serine proteases. Vaspin was first identified in 2005 in the visceral adipose tissue of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of obesity and type 2 diabetes. The discovery of Vaspin was driven by the need to understand better the molecular mechanisms linking obesity, insulin resistance, and metabolic syndrome. Since then, Vaspin has been studied extensively for its role in metabolism, inflammation, and potential therapeutic applications in treating metabolic diseases.

Protein Structure

The SERPINA12 gene encodes a protein comprising approximately 414 amino acids, with a molecular weight of around 45-50 kDa. Like other serpins, Vaspin exhibits a conserved structure characterized by three β-sheets and eight to nine α-helices, along with a reactive center loop (RCL). The RCL is a crucial structural feature of Vaspin, as it acts as a bait for target proteases. Upon interaction with a target protease, the RCL forms a stable complex that inhibits the protease's activity, thus preventing it from degrading specific substrates.

The crystal structure of Vaspin reveals that it adopts a typical serpin fold, which is essential for its inhibitory function. Notably, Vaspin's structure allows it to interact with serine proteases involved in metabolic regulation and inflammation, thereby exerting its biological effects. Post-translational modifications, such as glycosylation, may also play a role in stabilizing the protein and regulating its activity in the circulatory system.

Classification and Subtypes

SERPINA12 belongs to the A clade of the serpin superfamily, which includes other well-characterized serpins like α1-antitrypsin (SERPINA1) and antithrombin (SERPINC1). While many serpins are primarily involved in coagulation and inflammation, Vaspin is more specialized in metabolic regulation, particularly in the context of obesity and insulin resistance.

Vaspin is unique in that it is predominantly expressed in visceral adipose tissue, although it is also found in other tissues such as the liver, skin, and pancreas. To date, no distinct subtypes or isoforms of SERPINA12 have been identified. However, polymorphisms within the SERPINA12 gene can influence its expression levels and functional activity, contributing to variations in metabolic health among individuals.

Function and Biological Significance

Vaspin (SERPINA12) plays a crucial role in regulating glucose and lipid metabolism, making it a key player in the pathophysiology of obesity and type 2 diabetes. The primary function of Vaspin is to act as a serine protease inhibitor, modulating the activity of enzymes involved in the degradation of insulin-sensitizing molecules. By inhibiting these proteases, Vaspin enhances insulin sensitivity and promotes glucose uptake in adipocytes, thereby improving metabolic control.

One of the most significant proteases inhibited by Vaspin is kallikrein 7 (KLK7), an enzyme that degrades insulin receptor substrate-1 (IRS-1) and other proteins involved in insulin signaling. By inhibiting KLK7, Vaspin helps to preserve the integrity of insulin signaling pathways, thus promoting glucose uptake and reducing blood glucose levels.

Vaspin also exhibits anti-inflammatory properties, which further contribute to its beneficial effects on metabolic health. Inflammatory cytokines are known to impair insulin signaling and promote insulin resistance, a hallmark of type 2 diabetes. Vaspin counteracts this by inhibiting proteases that activate pro-inflammatory pathways, thereby reducing inflammation and improving insulin sensitivity.

Moreover, Vaspin has been shown to influence lipid metabolism by regulating the expression of genes involved in fatty acid synthesis and oxidation. This effect helps to prevent the accumulation of ectopic fat in tissues such as the liver and muscle, reducing the risk of developing non-alcoholic fatty liver disease (NAFLD) and other obesity-related complications.

The biological significance of Vaspin extends beyond its metabolic functions. It is also involved in the regulation of vascular homeostasis, with studies indicating that Vaspin can inhibit the proliferation and migration of vascular smooth muscle cells, processes that contribute to the development of atherosclerosis. This suggests that Vaspin may have a protective role in cardiovascular disease, particularly in individuals with metabolic syndrome.

Clinical Issues

Given its role in metabolic regulation, Vaspin has been studied as a potential biomarker for metabolic diseases, including obesity, type 2 diabetes, and cardiovascular disease. Serum levels of Vaspin have been found to correlate with body mass index (BMI), insulin resistance, and other markers of metabolic dysfunction. Elevated levels of Vaspin are often observed in obese individuals and those with type 2 diabetes, suggesting that Vaspin may serve as a compensatory mechanism to counteract metabolic stress.

However, the relationship between Vaspin levels and metabolic health is complex. While elevated Vaspin levels are generally associated with obesity and insulin resistance, some studies have suggested that Vaspin may have a protective role in the early stages of metabolic disease. For example, higher Vaspin levels have been linked to improved insulin sensitivity and better glycemic control in some populations.

Genetic studies have identified several polymorphisms in the SERPINA12 gene that are associated with altered Vaspin expression and metabolic outcomes. For instance, the rs2236242 polymorphism in the promoter region of SERPINA12 has been linked to an increased risk of obesity and insulin resistance in certain populations. These findings suggest that genetic variation in SERPINA12 may contribute to individual differences in susceptibility to metabolic diseases.

Vaspin has also been investigated as a potential therapeutic target for treating obesity and type 2 diabetes. Animal studies have shown that administration of recombinant Vaspin can improve glucose tolerance, reduce insulin resistance, and decrease body weight in obese mice. These findings have sparked interest in developing Vaspin-based therapies for metabolic diseases, although further research is needed to fully understand its therapeutic potential in humans.

Summary

SERPINA12, also known as Vaspin, is a serpin family member that plays a critical role in regulating glucose and lipid metabolism, inflammation, and vascular homeostasis. Vaspin is predominantly expressed in visceral adipose tissue and acts as a serine protease inhibitor, modulating the activity of enzymes involved in insulin signaling and metabolic regulation. Elevated Vaspin levels are often associated with obesity and type 2 diabetes, but its role in metabolic health is complex and may vary depending on the stage of disease and genetic background. Understanding the functions and regulation of SERPINA12 is essential for developing new strategies to combat metabolic diseases and improve overall health.