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Comprehensive lipidomics in apoM^(-/-) mice reveals an overall state of metabolic distress and attenuated hepatic lipid secretion into the circulation

查看全文 作  者:Yuanping [1]Shi;Sin Man [2]Lam;Hong [3]Liu;Guanghua [1]Luo;Jun [1]Zhang;Shuang [1]Yao;Jie [2]Li;Lu [1]Zheng;Ning [4]Xu;Xiaoying [3]Zhang;Guanghou [2]Shui 高影响力作者 机构地区:[1]Department of Comprehensive Laboratory,The Third Affiliated Hospital of Soochow University,Changzhou,213003,China;[2]Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing,100101,China;[3]Department of Cardiothoracic Surgery,The Third Affiliated Hospital of Soochow University,Changzhou,213003,China;[4]Section of Clinical Chemistry and Pharmacology,Institute of Laboratory Medicine,Lunds University,Klinikgatan 19,S–22185,Lund,Sweden高影响力机构 出  处:《Journal of Genetics and Genomics》索引2020年第47卷第9期,共12页高影响力期刊 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)。 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. 关 键 词:Nonalcoholic fatty liver disease Apolipoprotein M Lipid metabolism LIPIDOMICS LIPOPROTEIN
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