Visceral adipose tissue-derived serine protease inhibitor: A unique insulin-sensitizing adipocytokine in obesity
Visceral adipose tissue-derived serine protease inhibitor: A unique insulin-sensitizing adipocytokine in obesity
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DOI：
10.1073/pnas.0504703102
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发表时间：
2005-07-26
影响因子：
11.1
通讯作者：
Kanwar, YS
中科院分区：
文献类型：
--
作者：
Hida, K;Wada, J;Kanwar, YS
全球肥胖率迅速上升，而肥胖与糖尿病之间的联系仍然有些模糊。我们鉴定了一种脂肪细胞因子，称为内脏脂肪组织源性丝氨酸蛋白酶抑制剂（vaspin），它是丝氨酸蛋白酶抑制剂家族的成员。 Vaspin cDNA 是从大冢朗-埃文斯德岛脂肪 (OLETIF) 大鼠（一种患有 2 型糖尿病的腹部肥胖动物模型）的内脏白色脂肪组织 (WAT) 中分离出来的。大鼠、小鼠和人类 vaspin 分别由 392,394 和 395 个氨基酸组成；与 α(1)-抗胰蛋白酶表现出大约 40% 的同源性；并与丝氨酸蛋白酶抑制剂家族有关。 Vaspin 在 6 周时在大鼠中几乎检测不到，而在 30 周时在内脏 WAT 的脂肪细胞中高度表达，这是 OLETF 大鼠肥胖、体重和胰岛素水平达到峰值的年龄。 50周时，随着糖尿病的恶化和体重减轻，vaspin的组织表达及其血清水平降低。 OLETF 大鼠经胰岛素或胰岛素增敏剂吡格列酮治疗后，表达和血清水平恢复正常。对喂食高脂肪高蔗糖食物的肥胖 CRL:CD-1 (ICR) (ICR) 小鼠给予 vaspin 可以改善葡萄糖耐量和胰岛素敏感性，这反映在标准化的血清葡萄糖水平上。它还导致与胰岛素抵抗相关的基因表达改变的逆转，例如瘦素、抵抗素、TNF α、葡萄糖转运蛋白 4 和脂联素。在 DNA 芯片分析中，vaspin 处理导致 WAT 中大约 50% 的高脂肪高蔗糖诱导基因的表达逆转。这些发现表明，vaspin 在肥胖状态下针对 WAT 发挥胰岛素增敏作用。
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 (OLETIF) 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 approximate to 40% homology with alpha(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 insulin-sensitizing agent, pioglitazone, in OLETF rats. Administration of vaspin to obese CRL:CD-1 (ICR) (ICR) mice fed with high-fat high-sucrose 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 alpha, glucose transporter-4, and adiponectin. In DNA chip analyses, vaspin treatment resulted in the reversal of expression in approximate to 50% of the high-fat high-sucrose-induced genes in WATs. These findings indicate that vaspin exerts an insulin-sensitizing effect targeted toward WATs in states of obesity.