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_4 label "Selventa" provenance.
_3 value ", suggesting rhVaspin administration reverses the expression of the genes related to insulin resistance. Affymetrix Genechip revealed that rhVaspin administration reversed the mRNA levels in 49.9% and 52.8% of the genes with altered expression induced by HFHS chow in MES and SUB WATs, respectively. HFHS chow induced similar trends both in MES and SUB WATs that were characterized by negative values for the principal component (Fig. 6C). In contrast, MES WAT in mice with STD chow had positive value. The treatment of HFHS-chow-fed mice with vaspin increased the principal component values both in MES and SUB WATs (Fig. 6C). Hierarchical clustering analysis was consistent with changes in the principal component values dividing in two distinct groups, i.e., mice fed with the HFHS chow group and STD chow on separate branches of the dendrogram (Fig. 6D). Both vaspin-treated MES and SUB WATs were on the same branches as that of the STD diet group (Fig. 6D). Thus, it seems that vaspin treatment improves the insulin sensitivity by normalizing the gene expression mainly in the WATs. Discussion Serpins are a superfamily of proteins whose membership is based on the presence of a core domain consisting of three beta-sheets and nine alpha-helices. Literature data include ~500 serpins and a phylogenetic analysis divides serpins into 16 classes and 10 highly diverged ''orphans'' (29, 30). The structure of the cleaved alpha1- antitrypsin implies that serpins are ''suicidal inhibitors'' and the mechanism of proteinase inhibition may differ from other known classical inhibitors. The inhibitory activity of vaspin, though unknown but having a reactive site loop besides beta-sheets and alpha-helices (Figs. 1 and 4), would suggest that it belongs to serpin family. Traditionally, during inhibition the reactive site loop of alpha1- antitrypsin is cleaved by the target proteinases with the formation of a covalently bound serpin-proteinase complex and as a result the serpins undergo a conformational change (31). This conformational transition is related to inherent molecular flexibility in the serpins, but it also renders them susceptible to point mutations with the formation of anomalous intermolecular linkages and polymers. Of interest, some of the conformational diseases are related to the mutation in serpins and are known as serpinopathies (32). These disorders include those affecting the clotting, fibrinolytic, and complement systems; however, the role of the majority of serpins in various pathobiologic processes awaits further investigations (33). Vaspin expression, although specific to visceral adipose tissues, also has a circulating form, and the levels of both increase at the peak of obesity and insulin resistance, i.e., at 30 wk, and decrease with the worsening of diabetes in OLETF rats, i.e., at 50 wk (Figs. 1-3). Because administration of TZD, like insulin, significantly up-regulated vaspin mRNA and serum levels and maintained them until 50 wk of age, it would suggest the increase may be a compensatory response to antagonize the action of other unknown proteases up-regulated in obesity and in states of insulin resistance. In other words, the up-regulation of vaspin may have a defensive action against insulin resistance. To attest to such a contention, rhVaspin was administered to diet-induced obese mice, and this maneuver significantly improved insulin sensitivity and glucose tolerance (Fig. 5)." 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 "1.4" provenance.