Apolipoprotein M (apoM) participates in both high-density lipoprotein and cholesterol metabolism. Little is known about how apoM affects lipid composition of the liver and serum. In this study, we systemically investigated the effects of apoM on liver and plasma lipidomes and how apoM participates in lipid cycling, via apoM knockout in mice and the human SMMC-7721 cell line. We used integrated mass spectrometry-based lipidomics approaches to semiquantify more than 600 lipid species from various lipid classes, which include free fatty acids, glycerolipids, phospholipids, sphingolipids, glycosphingolipids, cholesterol, and cholesteryl esters (CEs), in apoM^-/- mouse. Hepatic accumulation of neutral lipids, including CEs, triacylglycerols, and diacylglycerols, was observed in apoM^-/- mice; while serum lipidomic analyses showed that, in contrast to the liver, the overall levels of CEs and saturated/monounsaturated fatty acids were markedly diminished. Furthermore, the level of ApoB-100 was dramatically increased in the liver, whereas significant reductions in both ApoB-100 and low-density lipoprotein (LDL) cholesterol were observed in the serum of apoM^-/- mice, which indicated attenuated hepatic LDL secretion into the circulation. Lipid profiles and proinflammatory cytokine levels indicated that apoM^-/- leads to hepatic steatosis and an overall state of metabolic distress. Taken together, these results revealed that apoM knockout leads to hepatic steatosis, impaired lipid secretion, and an overall state of metabolic distress.

载脂蛋白M（apoM）参与高密度脂蛋白和胆固醇代谢。关于apoM如何影响肝脏和血清脂质组成的知识鲜为人知。在这项研究中，我们系统地研究APOM的影响，对肝脏和血浆lipidomes以及如何参与APOM脂质循环，通过APOM在小鼠和人类的SMMC-7721细胞基因敲除。我们使用基于质谱的集成脂质组学方法对apoM ^-/-中的600多种来自各种脂质类别的脂质进行半定量，包括游离脂肪酸，甘油脂，磷脂，鞘脂，糖鞘脂，胆固醇和胆固醇酯（CEs）^-/-鼠。在apoM ^-/-小鼠中观察到肝中性脂质的积聚，包括CEs，三酰基甘油和二酰基甘油。血清脂质组学分析表明，与肝脏相比，CE和饱和/单不饱和脂肪酸的总体水平明显降低。此外，肝脏中ApoB-100的水平显着增加，而在apoM ^-/-小鼠的血清中观察到ApoB-100和低密度脂蛋白（LDL）胆固醇的显着降低，这表明肝脏LDL分泌减弱进入流通。脂质分布和促炎细胞因子水平表明apoM ^-/-导致肝脂肪变性和代谢窘迫的整体状态。综上所述，这些结果表明，apoM基因敲除可导致肝脂肪变性，脂质分泌受损和代谢窘迫的总体状态。