Ex vivo analysis of serum chemerin activity in murine models of obesity
Ex vivo analysis of serum chemerin activity in murine models of obesity
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DOI：
10.1016/j.cyto.2018.02.004
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发表时间：
2018-04-01
期刊：
影响因子：
3.8
通讯作者：
Buechler, Christa
中科院分区：
文献类型：
--
作者：
Haberl, Elisabeth M.;Pohl, Rebekka;Buechler, Christa
目的：Chemerin是一种脂肪因子，在炎症、脂肪形成以及葡萄糖和脂质稳态调节中发挥着既定作用。chemerin的细胞外蛋白水解加工产生一系列亚型，这些亚型在激活同源受体趋化因子样受体1（CMKLR 1）和G蛋白偶联受体1（GPR 1）的能力方面显著不同。在肥胖人群以及肥胖症的临床前啮齿动物模型中，已广泛报道了血清趋化蛋白总量的增加。然而，很少有信息是关于对应的，如果有的话，在总血清chemerin蛋白与chemerin biological.Methods的变化：总血清chemerin和离体CMKLR 1和GPR 1的激活进行了比较，使用两个广泛使用的小鼠肥胖模型：高脂饮食喂养（HFD）和瘦素缺乏症（ob/ob）。总血清chemerin水平和离体CMKLR 1和GPR 1激活显着诱导HFD。当用CMKLR 1而不是GPR 1测量时，生物活性比率（生物活性chemerin/总chemerin）也增加。相比之下，虽然ob/ob小鼠表现出增加的血清趋化蛋白总蛋白，离体受体活化观察到GPR 1，但不是CMKLR 1。两种受体的生物活性比均无变化。值得注意的是，GPR 1，而不是CMKLR 1的生物活性呈正相关脂肪组织inflammation.Conclusions：虽然增加血清chemerin总是一个一致的发现之间的啮齿动物肥胖模型，这可能无法准确地反映chemerin生物活性的变化，这是生物效应的主要决定因素。
Objectives: Chemerin is an adipokine with established roles in inflammation, adipogenesis and the regulation of glucose and lipid homeostasis. Extracellular proteolytic processing of chemerin generates a spectrum of isoforms that differ significantly with respect to the ability to activate the cognate receptors chemokine-like receptor 1 (CMKLR1) and G-protein-coupled receptor 1 (GPR1). Increased total serum chemerin has been widely reported in obese humans as well as in preclinical rodent models of adiposity. However, very little information is available regarding the correspondence, if any, of changes in total serum chemerin protein with chemerin bioactivity.Methods: Total serum chemerin and ex vivo CMKLR1 and GPR1 activation was compared using two widely used murine obesity models: high fat diet feeding (HFD) and leptin deficiency (ob/ob).Results: Total serum chemerin levels and ex vivo CMKLR1 and GPR1 activation were significantly induced in HFD. The bioactivity ratio (bioactive chemerin/total chemerin) was also increased when measured with CMKLR1, but not GPR1. In contrast, while ob/ob mice exhibited increased total serum chemerin protein, ex vivo receptor activation was observed with GPR1, but not CMKLR1. There was no change in bioactivity ratio for either receptor. Of note, GPR1 but not CMKLR1 bioactivity positively correlated with adipose tissue inflammation.Conclusions: While increased total serum chemerin is a consistent finding among rodent obesity models, this may not accurately reflect changes in chemerin bioactivity which is the major determinant of biological effects.