This Work Is Licensed under a Creative Commons Attribution-noncommercial 4.0 International License
This Work Is Licensed under a Creative Commons Attribution-noncommercial 4.0 International License
复制标题
本作品根据知识共享署名-非商业 4.0 国际许可证获得许可
DOI：
--
复制
发表时间：
--
期刊：
影响因子：
--
通讯作者：
K. Goralski
中科院分区：
文献类型：
--
作者：
Jay Toulany;S. Parlee;C. Sinal;K. Slayter;S. Mcneil;K. Goralski
在肥胖人群中，开放获取 CMKLR1 离体激活不会与血清总凯莫瑞成比例增加 摘要 Prochemerin 是脂肪因子凯莫瑞的无活性前体。蛋白水解过程是凯莫瑞原转化为活性凯莫瑞以及随后通过趋化因子样受体 1 (CMKLR1) 调节细胞过程所必需的。据报道，在肥胖人群中，血浆或血清凯莫瑞浓度升高以及凯莫瑞原的加工差异。这些变化对人类 CMKLR1 信号传导的影响尚不清楚。该初步研究的目的是开发一种细胞生物测定法来测量人血清中凯莫瑞对 CMKLR1 的激活，并表征肥胖如何在禁食和进食条件下改变 CMKLR1 的血清激活。从对照（N = 4，BMI 20-25）和肥胖（N = 4，BMI > 30）女性受试者在一整夜禁食（n = 2）后以及在 6 小时内食用早餐后定期（n = 7）采集血液样本。细胞 CMKLR1 发光报告基因测定和泛凯莫瑞 ELISA 分别用于测定 CMKLR1 激活和总凯莫瑞浓度。肥胖受试者的血清总凯莫瑞浓度（所有样本的平均值）高于对照组（17.9 ± 1.8 vs 10.9 ± 0.5 nM，P < 0.05），但两组的 CMKLR1 血清激活相似。与对照组相比，肥胖受试者的 CMKLR1 激活/总凯莫瑞比率较低（0.33 ± 0.04 vs 0.58 ± 0.05，P < 0.05）。早餐后，血清总凯莫瑞或 CMKLR1 激活与基线值没有差异。总之，肥胖血清中 CMKLR1 的激活与增加的总凯莫瑞浓度不匹配的意外观察表明，肥胖人血清中活性凯莫瑞的加工受损和/或降解增强。
Open Access CMKLR1 activation ex vivo does not increase proportionally to serum total chemerin in obese humans Abstract Prochemerin is the inactive precursor of the adipokine chemerin. Proteolytic processing is obligatory for the conversion of prochemerin into active chemerin and subsequent regulation of cellular processes via the chemokine-like receptor 1 (CMKLR1). Elevated plasma or serum chemerin concentrations and differential processing of prochemerin have been reported in obese humans. The impact of these changes on CMKLR1 signalling in humans is unknown. The objective of this pilot study was to develop a cellular bioassay to measure CMKLR1 activation by chemerin present in human serum and to characterise how obesity modifies serum activation of CMKLR1 under fasted and fed conditions. Blood samples were collected from control (N = 4, BMI 20–25) and obese (N = 4, BMI >30) female subjects after an overnight fast (n = 2) and at regular intervals (n = 7) following consumption of breakfast over a period of 6 h. A cellular CMKLR1-luminescent reporter assay and a pan-chemerin ELISA were used to determine CMKLR1 activation and total chemerin concentrations, respectively. Serum total chemerin concentration (averaged across all samples) was higher in obese vs control subjects (17.9 ± 1.8 vs 10.9 ± 0.5 nM, P < 0.05), but serum activation of CMKLR1 was similar in both groups. The CMKLR1 activation/total chemerin ratio was lower in obese vs control subjects (0.33 ± 0.04 vs 0.58 ± 0.05, P < 0.05). After breakfast, serum total chemerin or CMKLR1 activation did not differ from baseline values. In conclusion, the unexpected observation that obese serum activation of CMKLR1 did not match increased total chemerin concentrations suggests impaired processing to and/or enhanced degradation of active chemerin in serum of obese humans.