Sin Man Lam
Hong Liu
Guanghua Luo
Jun Zhang
Shuang Yao
Jie Li
Lu Zheng
Ning Xu
Xiaoying Zhang
Guanghou Shui
aDepartment of Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
bInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
cDepartment of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
dSection of Clinical Chemistry and Pharmacology, Institute of Laboratory Medicine, Lunds University, Klinikgatan 19, S–22185, Lund, Sweden
More InformationCorresponding author: E-mail address: zhangxy6689996@163.com (Xiaoying Zhang);E-mail address: ghshui@genetics.ac.cn (Guanghou Shui)
Publish Date:2020-09-25
Abstract
Abstract
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 ofapoM 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.Keywords: Nonalcoholic fatty liver disease,
Apolipoprotein M,
Lipid metabolism,
Lipidomics,
Lipoprotein
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