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

Yuanping Shi; Sin Man Lam; Hong Liu; Guanghua Luo; Jun Zhang; Shuang Yao; Jie Li; Lu Zheng; Ning Xu; Xiaoying Zhang; Guanghou Shui

doi:10.1016/j.jgg.2020.08.003

Volume 47 Issue 9

Sep. 2020

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Article Navigation > Journal of Genetics and Genomics > 2020 > 47(9): 523-534

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

doi: 10.1016/j.jgg.2020.08.003

a
Department of Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
b
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
c
Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
d
Section of Clinical Chemistry and Pharmacology, Institute of Laboratory Medicine, Lunds University, Klinikgatan 19, S–22185, Lund, Sweden

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Corresponding 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.
- Nonalcoholic fatty liver disease,
- Apolipoprotein M,
- Lipid metabolism,
- Lipidomics,
- Lipoprotein

These authors equally contributed to this work.

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References(58)

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