Sell Henrike, Laurencikiene Jurga, Taube Annika, Eckardt Kristin, Cramer Andrea, Horrighs Angelika, Arner Peter, Eckel Jürgen
Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.
Diabetes. 2009 Dec;58(12):2731-40. doi: 10.2337/db09-0277. Epub 2009 Aug 31.
Chemerin is an adipokine that affects adipogenesis and glucose homeostasis in adipocytes and increases with BMI in humans. This study was aimed at investigating the regulation of chemerin release and its effects on glucose metabolism in skeletal muscle cells.
Human skeletal muscle cells were treated with chemerin to study insulin signaling, glucose uptake, and activation of stress kinases. The release of chemerin was analyzed from in vitro differentiated human adipocytes and adipose tissue explants from 27 lean and 26 obese patients.
Human adipocytes express chemerin and chemokine-like receptor 1 (CMKLR1) differentiation dependently and secrete chemerin (15 ng/ml from 10(6) cells). This process is slightly but significantly increased by tumor necrosis factor-alpha and markedly inhibited by >80% by peroxisome proliferator-activated receptor-gamma activation. Adipose tissue explants from obese patients are characterized by significantly higher chemerin secretion compared with lean control subjects (21 and 8 ng from 10(7) cells, respectively). Chemerin release is correlated with BMI, waist-to-hip ratio, and adipocyte volume. Furthermore, higher chemerin release is associated with insulin resistance at the level of lipogenesis and insulin-induced antilipolysis in adipocytes. Chemerin induces insulin resistance in human skeletal muscle cells at the level of insulin receptor substrate 1, Akt and glycogen synthase kinase 3 phosphorylation, and glucose uptake. Furthermore, chemerin activates p38 mitogen-activated protein kinase, nuclear factor-kappaB, and extracellular signal-regulated kinase (ERK)-1/2. Inhibition of ERK prevents chemerin-induced insulin resistance, pointing to participation of this pathway in chemerin action.
Adipocyte-derived secretion of chemerin may be involved in the negative cross talk between adipose tissue and skeletal muscle contributing to the negative relationship between obesity and insulin sensitivity.
chemerin是一种脂肪因子，可影响脂肪细胞的脂肪生成和葡萄糖稳态，且在人类中随体重指数（BMI）增加而升高。本研究旨在探讨chemerin释放的调节及其对骨骼肌细胞葡萄糖代谢的影响。
用chemerin处理人骨骼肌细胞，以研究胰岛素信号传导、葡萄糖摄取及应激激酶的激活情况。分析了来自27名瘦人和26名肥胖患者的体外分化人脂肪细胞及脂肪组织外植体中chemerin的释放情况。
人脂肪细胞分化依赖性地表达chemerin和趋化因子样受体1（CMKLR1），并分泌chemerin（10⁶个细胞分泌15 ng/ml）。肿瘤坏死因子-α可轻微但显著增加这一过程，而过氧化物酶体增殖物激活受体-γ激活则可使其显著抑制>80%。与瘦对照受试者相比，肥胖患者的脂肪组织外植体中chemerin分泌显著更高（分别为10⁷个细胞分泌21 ng和8 ng）。chemerin释放与BMI、腰臀比及脂肪细胞体积相关。此外，chemerin释放较高与脂肪生成水平的胰岛素抵抗及脂肪细胞中胰岛素诱导的抗脂解作用相关。Chemerin在胰岛素受体底物1、Akt和糖原合酶激酶3磷酸化及葡萄糖摄取水平诱导人骨骼肌细胞产生胰岛素抵抗。此外，chemerin可激活p38丝裂原活化蛋白激酶、核因子-κB及细胞外信号调节激酶（ERK）-1/2。抑制ERK可防止chemerin诱导的胰岛素抵抗，表明该信号通路参与了chemerin的作用。
脂肪细胞来源的chemerin分泌可能参与了脂肪组织与骨骼肌之间的负性相互作用，导致肥胖与胰岛素敏感性之间的负相关关系。
