There is a rapid global rise in obesity, and the link between obesity and diabetes remains somewhat obscure. We identified an adipocytokine, designated as visceral adipose tissue-derived serpin (vaspin), which is a member of serine protease inhibitor family. Vaspin cDNA was isolated by from visceral white adipose tissues (WATs) of Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model of abdominal obesity with type 2 diabetes. Rat, mouse, and human vaspins are made up of 392, 394, and 395 amino acids, respectively; exhibit Ϸ40% homology with ␣1-antitrypsin; and are related to serine protease inhibitor family. Vaspin was barely detectable in rats at 6 wk and was highly expressed in adipocytes of visceral WATs at 30 wk, the age when obesity, body weight, and insulin levels peak in OLETF rats. The tissue expression of vaspin and its serum levels decrease with worsening of diabetes and body weight loss at 50 wk. The expression and serum levels were normalized with the treatment of insulin or insulinsensitizing agent, pioglitazone, in OLETF rats. Administration of vaspin to obese CRL:CD-1 (ICR) (ICR) mice fed with high-fat highsucrose chow improved glucose tolerance and insulin sensitivity reflected by normalized serum glucose levels. It also led to the reversal of altered expression of genes relevant to insulin resistance, e.g., leptin, resistin, TNF␣, glucose transporter-4, and adiponectin. In DNA chip analyses, vaspin treatment resulted in the reversal of expression in Ϸ50% of the high-fat high-sucroseinduced genes in WATs. These findings indicate that vaspin exerts an insulin-sensitizing effect targeted toward WATs in states of obesity.metabolic syndrome ͉ diabetes ͉ insulin resistance ͉ mesenteric ͉ white adipose tissue

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OBJECTIVE:To investigate whether the changes in vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before and after weight reduction in Japanese overweight men are associated with changes in body mass index (BMI), visceral, subcutaneous fat, VO 2 and work rate (WR) at ventilatory threshold (VT). DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: In total, 30 Japanese overweight men (BMI, 29.072.2 kg/m 2 ) and 31 normal-weight men (BMI, 22.571.6 kg/m 2 ) at baseline were enrolled: 30 overweight men (BMI, 29.072.2 kg/m 2 ) were further enrolled into a 6-month exercise program. MEASUREMENTS: Fat distribution evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, angiogenic peptides including VEGF and bFGF, exercise tests at baseline and after 6 months. RESULTS: In normal-weight and overweight subjects at baseline, VEGF positively correlated with S area (r ¼ 0.350, P ¼ 0.007) but not with V area. In contrast, bFGF negatively correlated with BMI (r ¼ À0.619, Po0.001), S (r ¼ À0.457, Po0.001) and V areas (r ¼ À0.466, Po0.001). By intervention with exercise education, 30 overweight subjects showed reduction in BMI (29.072.2 to 28.072.0, Po0.001), V and S areas, increase in VO 2 and WR at VT, increase in bFGF (9.2175.82-21.277.04 ng/ ml, Po0.001), and no change in VEGF (1.4570.72-1.8870.52 ng/ml, P ¼ 0.016). The stepwise multiple regression analysis revealed that DBMI (b ¼ À6.052) and DVO 2 (b ¼ 2.806) were independently related to DbFGF (Po0.001) and all other variables including DS area, and DV area, and DWR did not enter the equation at significant levels. CONCLUSION: The present study indicated a negative correlation between serum bFGF levels and BMI at baseline as well as an association of DBMI and DVO 2 with DbFGF after exercise intervention. The exercise-induced elevation of bFGF may be beneficial in the prevention of the atherosclerosis in overweight subjects.