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_4 label "Selventa" provenance.
_3 value "Recently, there has been a worldwide increase in the incidence of obesity associated with a metabolic syndrome known as type 2 diabetes, the development of which seems to be as a result of high-caloric diet intake and physical inactivity (1, 2); and predicted estimates suggest that the population with this syndrome may double to ~300 million by the year 2025 (3). One of the critical determinants for the development of this obesity may be an increase in the regional distribution of body fat, i.e., abdominal obesity. The latter often shows clustering of atherogenic risk factors (4, 5), i.e., hypertension, dyslipidemia, alterations in coagulation and inflammatory cytokine profiles, and hyperinsulinemic insulin resistance. As a consequence, there is an expected increase in morbidity and mortality of cardiovascular disease (6-9). Vigorous efforts have been made to delineate the relationship between increased adiposity and insulin resistance. In this regard, some molecules, including free fatty acids, leptin (10, 11), TNF-alpha (12, 13), acylation-stimulating protein (14, 15), adiponectin (16, 17), and resistin (18), which are secreted by the adipocytes, may modulate the sensitivity of insulin, the action of which activates multiple signaling events after phosphorylation of insulin receptor and several other molecules in type 2 diabetes (19, 20). To address the causal relationship between insulin resistance and obesity, various animal models, e.g., Otsuka Long-Evans Tokushima fatty (OLETF) rats, have been used by many investigators. The OLETF rat is an animal model of type 2 diabetes, which is characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia (21). Previously, we isolated a ~135-bp cDNA fragment during differential screening of the genes upregulated in visceral adipose tissues of obese OLETF rats and down-regulated in nonobese and diabetes-resistant Long-Evans Tokushima Otsuka (LETO) rats (22). This cDNA fragment exhibited partial homology with the serine protease inhibitor belonging to the serine protease inhibitor (serpin) family. In this study, we describe the isolation of the full-length cDNA of this potential inhibitor, designated as \"vaspin\" (visceral adipose tissue-derived serpin). In addition, preparation of its putative protein and characterization of its biological properties by using in vitro and in vivo rat and mouse model systems are included in this communication. Vaspin Is a Visceral Adipose Tissue-Derived Serpin. The rat, mouse, and human vaspin cDNAs had ORFs of 1,236, 1,242, and 1,245 nucleotides, respectively (Fig. 1A). The putative proteins included 412, 414, and 415 amino. The analysis of the deduced amino acid sequence of rat, mouse, and human orthologs predicted a hydrophobic N-terminal signal peptide (underscored), and N-terminal Edman sequencing revealed that mouse vaspin protein begins at the Leu-21 residue. The reactive loop site (boxed) extends from 364 to 379 residues (Fig. 1A). Homology analyses indicated that vaspin has 40.5% identity with alpha1-antitrypsin. Automated protein structure homologymodeling by SWISS-MODEL (http://swiss-model.expasy.org) predicted the presence of three beta-sheets (blue), nine alpha-helices (red), and one reactive center loop (yellow), features characteristic of serpin gene family (Fig. 1B). A single transcript was observed in visceral WATs of 30-wk-old obese OLETF rats [VIS(OLTEF)], and it was absent in 6-wk-old lean LETO rats [VIS(LETO)] and in subdermal (SUB) and brown fatty tissues (Fig. 1C). No vaspin mRNA expression was observed in other nonadipose tissues from OLETF rats, suggesting its role in abdominal obesity as observed in this metabolic syndrome. Similarly, no mRNA transcript was observed in nonadipose tissues from human and mouse organs (data not shown). Regulation of Vaspin Gene Expression in Genetically Obese OLETF Rats. To investigate the regulation of vaspin gene exp..." provenance.
_3 wasQuotedFrom 16030142 provenance.
assertion hadPrimarySource 16030142 provenance.
large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
large_corpus.bel description "Approximately 61,000 statements." provenance.
assertion wasDerivedFrom large_corpus.bel provenance.
assertion wasDerivedFrom _3 provenance.
large_corpus.bel authoredBy _4 provenance.
large_corpus.bel version "20131211" provenance.