Comprehensive lipidomics in apoM-/- mice reveals an overall state of metabolic distress and attenuated hepatic lipid secretion into the circulation |
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| Institution: | 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;1. Center for Laboratory Medicine, University Hospital Münster, Germany;2. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany;3. Department of Neuroscience - Unit of Pharmacology, University of Parma, Parma, Italy;4. Department of Biomedical, Metabolic and Neural Sciences – Unit of Endocrinology, University of Modena and Reggio Emilia, Modena, Italy;5. Experimental and Clinical Haemostasis, Department of Anaesthesiology and Intensive Care, University Hospital Münster, Münster, Germany;6. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark;7. Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark;1. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark;2. Department of Biomedical Sciences, University of Copenhagen, Denmark;3. Department of Diabetic Complications Biology, Novo Nordisk A/S, Måløv, Denmark;4. Department of Biostatistics, University of Copenhagen, Denmark;5. Department of Clinical Medicine, University of Copenhagen, Denmark;1. Fibrosis Research Center, Mount Sinai-National Jewish Respiratory Institute, Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;2. Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA;3. Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA;4. Department of Clinical Biochemistry, Righosiptalet, and Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark;5. Aarhus University, 8000 Aarhus, Denmark;6. Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;1. Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China;2. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;3. Department of Clinical Medicine, Bengbu Medical College, Bengbu 233000, China;4. LipidALL Technologies Company Limited, Changzhou, 213022 Jiangsu Province, China |
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| 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 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. |
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| Keywords: | Nonalcoholic fatty liver disease Apolipoprotein M Lipid metabolism Lipidomics Lipoprotein |
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