Chemerin is a novel adipokine associated with obesity and metabolic syndrome

Chemerin is a novel adipokine associated with obesity and metabolic syndrome
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DOI:
10.1210/en.2007-0175
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发表时间:
2007-10-01
期刊:
影响因子:
4.8
通讯作者:
Segal, David
Segal, David
中科院分区:
医学2区
文献类型:
--
作者:
Bozaoglu, Kiymet;Bolton, Kristy;Segal, David

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可溶性蛋白激素是许多代谢过程的关键调节因子,包括食物摄入和胰岛素敏感性。我们使用信号序列陷阱来识别肥胖和2型糖尿病(T2D)动物模型Psammomys obesus中编码分泌或膜结合蛋白的基因。利用这个信号序列陷阱,我们确定趋化因子趋化素是一种新的脂肪因子。趋化素及其受体趋化因子样受体1 (CMKLR1)的基因表达在肥胖和2型糖尿病P. obesus的脂肪组织中显著高于瘦弱、血糖正常的P. obesus。脂肪组织分离证实chemerin主要在脂肪细胞中表达,而CMKLR1在脂肪细胞和脂肪组织的基质血管细胞中均有表达。在3T3-L1脂肪细胞中,趋化素在分化过程中被显著诱导,而CMKLR1在分化过程中被下调。采用ELISA法测定了114例T2D患者和142例正常糖耐量对照者血浆样本的血清趋化素水平。血浆趋化素水平在T2D患者和正常对照组之间无显著差异。然而,在正常的糖耐量受试者中,血浆趋化素水平与体重指数、循环甘油三酯和血压显著相关。在这里,我们首次报道了趋化素是一种脂肪因子,并且循环中的趋化素水平与代谢综合征的几个关键方面有关。
Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.