Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action
Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action
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DOI：
10.1152/ajpendo.00572.2004
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发表时间：
2006-06-01
影响因子：
5.1
通讯作者：
Gong, Da-Wei
中科院分区：
文献类型：
--
作者：
Yang, Rong-Ze;Lee, Mi-Jeong;Gong, Da-Wei
与外周[皮下]肥胖相比，中枢（内脏）肥胖与胰岛素抵抗、2型糖尿病和心血管疾病的关系更为密切，但这种病理生理差异的潜在机制在很大程度上尚不清楚。为了了解这种差异的分子基础，我们从人类大网膜脂肪cDNA文库中测序了10,437个表达序列标签（est），并发现了一种新的内脏脂肪库特异性分泌蛋白，我们将其命名为大网膜蛋白（omentin）。Omentin ESTs比cDNA文库中许多已知的脂肪基因（如perilipin、脂联素和瘦素）更为丰富。蛋白序列分析表明，大网膜mRNA编码一个313个氨基酸的肽，包含一个分泌信号序列和一个纤维蛋白原相关结构域。Northern分析表明，网膜mRNA主要在内脏脂肪组织中表达，在人类和恒河猴的sc脂肪库中几乎检测不到。实时荧光定量PCR结果显示，大网膜脂肪组织中基质血管细胞中有大网膜mRNA的表达，而脂肪细胞中无大网膜mRNA的表达，大网膜细胞中大网膜mRNA的表达量比大网膜脂肪细胞少150倍。因此，网膜蛋白被分泌到网膜培养液中，而sc脂肪培养液中则没有。Western blot法检测人血清中Omentin。体外添加重组网膜蛋白对sc （47%, n = 9, P = 0.003）和网膜（30%,n = 3, P < 0.05）人脂肪细胞的葡萄糖摄取没有影响，但胰岛素刺激的葡萄糖摄取增强了。在没有胰岛素和存在胰岛素的情况下，Omentin增加Akt磷酸化。综上所述，网膜蛋白是一种新的脂肪因子，在人类网膜脂肪组织中表达，并可能调节胰岛素的作用。
Central ( visceral) obesity is more closely associated with insulin resistance, type 2 diabetes, and cardiovascular disease than is peripheral [ subcutaneous (sc)] obesity, but the underlying mechanism for this pathophysiological difference is largely unknown. To understand the molecular basis of this difference, we sequenced 10,437 expressed sequence tags ( ESTs) from a human omental fat cDNA library and discovered a novel visceral fat depot-specific secretory protein, which we have named omentin. Omentin ESTs were more abundant than many known adipose genes, such as perilipin, adiponectin, and leptin in the cDNA library. Protein sequence analysis indicated that omentin mRNA encodes a peptide of 313 amino acids, containing a secretory signal sequence and a fibrinogen-related domain. Northern analysis demonstrated that omentin mRNA was predominantly expressed in visceral adipose tissue and was barely detectable in sc fat depots in humans and rhesus monkeys. Quantative real-time PCR showed that omentin mRNA was expressed in stromal vascular cells, but not fat cells, isolated from omental adipose tissue, with > 150-fold less in sc cell fractions. Accordingly, omentin protein was secreted into the culture medium of omental, but not sc, fat explants. Omentin was detectable in human serum by Western blot analysis. Addition of recombinant omentin in vitro did not affect basal but enhanced insulin-stimulated glucose uptake in both sc (47%, n = 9, P = 0.003) and omental (similar to 30%, n = 3, P < 0.05) human adipocytes. Omentin increased Akt phosphorylation in the absence and presence of insulin. In conclusion, omentin is a new adipokine that is expressed in omental adipose tissue in humans and may regulate insulin action.