To explore the metabolic effect of chemerin, adipose-specific chemerin knockout (adipo-chemerin^−/−) male mice were established and fed with 5-week normal diet (ND) or high-fat diet (HFD), and then the glycolipid metabolism index was measured and epididymal adipose tissue metabolomics detected using untargeted LC–tandem mass spectrometry (LC–MS/MS). Under HFD, adipo-chemerin^−/− mice showed improved glycolipid metabolism (decreased total cholesterol, low-density lipoprotein-cholesterol, insulin and Homeostasis Model Assessment of Insulin Resistance) compared with flox (control) mice. Furthermore, orthogonal partial least squares-discriminant analysis score plots identified separation of metabolites between adipo-chemerin^−/− mice and flox mice fed ND and HFD. Under HFD, 28 metabolites were significantly enhanced in adipo-chemerin^−/− mice, and pathway enrichment analysis suggested strong relationship of the differential metabolites with arginine and proline metabolism, phenylalanine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis, which were directly or indirectly related to lipid metabolism, inflammation and oxidative stress. Under ND, taurine was increased in adipo-chemerin^−/− mice, resulting in taurine and hypotaurine metabolism and primary bile acid biosynthesis. In conclusion, the improved effect of chemerin knockdown on the glycolipid metabolism of HFD-feeding male mice might be associated with the increases in differential metabolites and metabolic pathways involved in lipid metabolism, inflammation and oxidative stress, which provided insights into the mechanism of chemerin from a metabolomics aspect.

中文翻译：

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脂肪特异性凯莫瑞基因敲除改变了正常和高脂饮食条件下脂肪组织的代谢组学特征：非靶向液相色谱-串联质谱代谢组学方法的应用

为了探索凯莫瑞的代谢作用，建立了脂肪特异性凯莫瑞敲除（adipo-chemerin ^-/-）雄性小鼠，喂食5周正常饮食（ND）或高脂饮食（HFD），然后进行糖脂代谢。使用非靶向LC-串联质谱（LC-MS / MS）测量指数并检测附睾脂肪组织代谢组学。在 HFD 下，与 flox（对照）小鼠相比，脂肪凯莫瑞^-/-小鼠的糖脂代谢得到改善（总胆固醇、低密度脂蛋白胆固醇、胰岛素和胰岛素抵抗的稳态模型评估降低）。此外，正交偏最小二乘判别分析得分图确定了脂肪-凯莫瑞之间代谢物的分离^-/-喂食ND和HFD的小鼠和flox小鼠。在 HFD 下，adipo-chemerin ^-/-小鼠的 28 种代谢物显着增强，通路富集分析表明，差异代谢物与精氨酸和脯氨酸代谢、苯丙氨酸代谢以及苯丙氨酸、酪氨酸和色氨酸生物合成密切相关，直接或间接与脂质代谢、炎症和氧化应激有关。在 ND 下，脂肪-凯莫瑞中的牛磺酸增加^-/-小鼠，导致牛磺酸和亚牛磺酸代谢和初级胆汁酸生物合成。总之，chemerin 敲低对 HFD 喂养雄性小鼠糖脂代谢的改善作用可能与参与脂质代谢、炎症和氧化应激的差异代谢物和代谢途径的增加有关，这为从代谢组学方面。