摘要
Apolipoprotein M(apoM) participates in both high-density lipoprotein and cholesterol metabolism. Little is known about how apo M affects lipid composition of the liver and serum. In this study, we systemically investigated the effects of apo M on liver and plasma lipidomes and how apo M participates in lipid cycling, via apo M 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 apo M^(-/-)mouse. Hepatic accumulation of neutral lipids, including CEs, triacylglycerols, and diacylglycerols, was observed in apo M^(-/-)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 Apo B-100 was dramatically increased in the liver, whereas significant reductions in both Apo B-100 and low-density lipoprotein(LDL) cholesterol were observed in the serum of apo M^(-/-)mice, which indicated attenuated hepatic LDL secretion into the circulation. Lipid profiles and proinflammatory cytokine levels indicated that apo M^(-/-)leads to hepatic steatosis and an overall state of metabolic distress. Taken together, these results revealed that apo M knockout leads to hepatic steatosis, impaired lipid secretion, and an overall state of metabolic distress.
基金
supported by the National Natural Science Foundation of China(81370372)
the National Key R&D Program of China under award number 2018YFA0506900 and 2018YFA 0800901
the Natural Science Foundation of Jiangsu Province(BK20191158,BK20151179)
Jiangsu Provincial Youth Medicine Key Talent Project(QNRC2016282)
Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX202680)
Major Science and Technology Project of Changzhou Health Commission(no.ZD202009)
the International Cooperation Foundation of Changzhou(CZ20160013,CZ20190022)。
