首页> 外文期刊>American Journal of Physiology >Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action.
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Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action.

机译:omentin鉴定为人类脂肪组织中一种新型的储库特异性脂肪因子:在调节胰岛素作用中的可能作用。

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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 (approximately 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.
机译:中枢性(内脏)肥胖与胰岛素抵抗,2型糖尿病和心血管疾病的关系比周围性[皮下(sc)]肥胖更为密切,但是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,我们从人网膜脂肪cDNA文库中测序了10437个表达的序列标签(EST),并发现了一种新型的内脏脂肪储库特异性分泌蛋白,我们将其命名为omentin。 Omentin EST比cDNA文库中许多已知的脂肪基因(例如周脂素,脂联素和瘦素)丰富。蛋白质序列分析表明,omentin 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与纤维蛋白原相关的结构域。 Northern分析表明,omentin mRNA主要在内脏脂肪组织中表达,在人和恒河猴的sc脂肪库中几乎检测不到。实时定量PCR显示,从网膜脂肪组织中分离出的网膜蛋白mRNA在基质血管细胞中表达,但在脂肪细胞中不表达,sc细胞组分的表达减少了150倍以上。因此,网膜蛋白被分泌到网膜脂肪而不是皮脂外植体的培养基中。通过蛋白质印迹分析在人血清中可检测到网膜蛋白。体外添加重组omentin不会影响基础脂肪,但在sc(47%,n = 9,P = 0.003)和omental(约30%,n = 3,P <0.05)人脂肪细胞中,胰岛素刺激的葡萄糖摄取都会增加。在没有胰岛素存在的情况下,网膜蛋白可增加Akt磷酸化。总之,omentin是一种新的脂肪因子,在人的大网膜脂肪组织中表达,并可能调节胰岛素的作用。

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