Bozaoglu Kiymet, Bolton Kristy, McMillan Janine, Zimmet Paul, Jowett Jeremy, Collier Greg, Walder Ken, Segal David
Metabolic Research Unit, School of Exercise and Nutrition Sciences, Deakin University, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia.
Endocrinology. 2007 Oct;148(10):4687-94. doi: 10.1210/en.2007-0175. Epub 2007 Jul 19.
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.
可溶性蛋白激素是包括食物摄入和胰岛素敏感性在内的多种代谢过程的关键调节因子。我们利用信号序列捕获技术，在肥胖和2型糖尿病（T2D）动物模型——肥胖沙鼠中，鉴定出编码分泌型或膜结合型蛋白的基因。利用这种信号序列捕获技术，我们确定趋化因子chemerin是一种新型脂肪因子。与瘦的、血糖正常的肥胖沙鼠相比，肥胖和2型糖尿病肥胖沙鼠脂肪组织中chemerin及其受体趋化因子样受体1（CMKLR1）的基因表达显著更高。对肥胖沙鼠脂肪组织进行分级分离证实，chemerin主要在脂肪细胞中表达，而CMKLR1在脂肪组织的脂肪细胞和基质血管细胞中均有表达。在3T3-L1脂肪细胞中，chemerin在分化过程中显著诱导表达，而CMKLR1在分化过程中下调。通过酶联免疫吸附测定法（ELISA）检测了114名2型糖尿病患者和142名糖耐量正常对照者的人血浆样本中的血清chemerin水平。2型糖尿病患者和正常对照者之间的血浆chemerin水平无显著差异。然而，在糖耐量正常的受试者中，血浆chemerin水平与体重指数、循环甘油三酯和血压显著相关。在此我们首次报道，chemerin是一种脂肪因子，其循环水平与代谢综合征的几个关键方面相关。
