{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:57:58Z","timestamp":1792623478308,"version":"4.5.0"},"reference-count":65,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,9]],"date-time":"2023-04-09T00:00:00Z","timestamp":1680998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004694","name":"Kaohsiung Medical University","doi-asserted-by":"publisher","award":["KMU-DK(A)111002"],"award-info":[{"award-number":["KMU-DK(A)111002"]}],"id":[{"id":"10.13039\/501100004694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004694","name":"Kaohsiung Medical University","doi-asserted-by":"publisher","award":["NSTC-111-2320-B-037-023-"],"award-info":[{"award-number":["NSTC-111-2320-B-037-023-"]}],"id":[{"id":"10.13039\/501100004694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004694","name":"Kaohsiung Medical University","doi-asserted-by":"publisher","award":["NSTC-111-2628-B-214-002-"],"award-info":[{"award-number":["NSTC-111-2628-B-214-002-"]}],"id":[{"id":"10.13039\/501100004694","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taiwan National Science and Technology Council","award":["KMU-DK(A)111002"],"award-info":[{"award-number":["KMU-DK(A)111002"]}]},{"name":"Taiwan National Science and Technology Council","award":["NSTC-111-2320-B-037-023-"],"award-info":[{"award-number":["NSTC-111-2320-B-037-023-"]}]},{"name":"Taiwan National Science and Technology Council","award":["NSTC-111-2628-B-214-002-"],"award-info":[{"award-number":["NSTC-111-2628-B-214-002-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite the availability and use of numerous cholesterol-lowering drugs, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality globally. Many researchers have focused their effort on identifying modified lipoproteins. However, lipid moieties such as lysophosphatidylcholine (LPC) and ceramide (CER) contribute to atherogenic events. LPC and CER both cause endothelial mitochondrial dysfunction, leading to fatty acid and triglyceride (TG) accumulation. In addition, they cause immune cells to differentiate into proinflammatory phenotypes. To uncover alternative therapeutic approaches other than cholesterol- and TG-lowering medications, we conducted untargeted lipidomic investigations to assess the alteration of lipid profiles in apolipoprotein E knockout (apoE\u2212\/\u2212) mouse model, with or without feeding a high-fat diet (HFD). Results indicated that, in addition to hypercholesterolemia and hyperlipidemia, LPC levels were two to four times higher in apoE\u2212\/\u2212 mice compared to wild-type mice in C57BL\/6 background, regardless of whether they were 8 or 16 weeks old. Sphingomyelin (SM) and CER were elevated three- to five-fold in apoE\u2212\/\u2212 mice both at the basal level and after 16 weeks when compared to wild-type mice. After HFD treatment, the difference in CER levels elevated more than ten-fold. Considering the atherogenic properties of LPC and CER, they may also contribute to the early onset of atherosclerosis in apoE\u2212\/\u2212 mice. In summary, the HFD-fed apoE\u2212\/\u2212 mouse shows elevated LPC and CER contents and is a suitable model for developing LPC- and CER-lowering therapies.<\/jats:p>","DOI":"10.3390\/ijms24086956","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"6956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Untargeted Lipidomic Profiling Reveals Lysophosphatidylcholine and Ceramide as Atherosclerotic Risk Factors in apolipoprotein E Knockout Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Shi-Hui","family":"Law","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-8392","authenticated-orcid":false,"given":"Hua-Chen","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, College of Medicine, I-Shou University, Kaohsiung 84001, Taiwan"},{"name":"Center for Lipid Biosciences, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Ming","family":"Ke","sequence":"additional","affiliation":[{"name":"Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetha","family":"Kamatam","sequence":"additional","affiliation":[{"name":"Department of Studies in Biochemistry and Molecular Biology, University of Mysore, Manasagangothri, Mysuru 570006, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopal Kedihithlu","family":"Marathe","sequence":"additional","affiliation":[{"name":"Department of Studies in Biochemistry and Molecular Biology, University of Mysore, Manasagangothri, Mysuru 570006, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2112-2085","authenticated-orcid":false,"given":"Vinoth Kumar","family":"Ponnusamy","sequence":"additional","affiliation":[{"name":"Department of Medicinal and Applied Chemistry, Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2547-0987","authenticated-orcid":false,"given":"Liang-Yin","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Center for Lipid Biosciences, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan"},{"name":"Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.jacc.2022.11.005","article-title":"The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health","volume":"80","author":"Vaduganathan","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E84","DOI":"10.5888\/pcd19.220347","article-title":"Global Responses to Prevent, Manage, and Control Cardiovascular Diseases","volume":"19","author":"Coronado","year":"2022","journal-title":"Prev. Chronic. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1161\/01.cir.0000437741.48606.98","article-title":"2013 ACC\/AHA guideline on the assessment of cardiovascular risk: A report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"129","author":"Goff","year":"2014","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1161\/01.cir.0000437738.63853.7a","article-title":"2013 ACC\/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"129","author":"Stone","year":"2014","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1016\/j.jacc.2017.10.024","article-title":"Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors","volume":"70","author":"Fuster","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s40256-017-0259-7","article-title":"Management of Statin Intolerance in 2018: Still More Questions Than Answers","volume":"18","author":"Toth","year":"2018","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"153833","DOI":"10.1016\/j.phymed.2021.153833","article-title":"Study on the new anti-atherosclerosis activity of different Herba patriniae through down-regulating lysophosphatidylcholine of the glycerophospholipid metabolism pathway","volume":"94","author":"Su","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1615664","article-title":"Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease","volume":"376","author":"Sabatine","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"164","DOI":"10.18773\/austprescr.2016.060","article-title":"PCSK9 inhibitors\u2014Mechanisms of action","volume":"39","author":"Page","year":"2016","journal-title":"Aust. Prescr."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Liu, C., Chen, J., Chen, H., Zhang, T., He, D., Luo, Q., Chi, J., Hong, Z., Liao, Y., and Zhang, S. (2022). PCSK9 Inhibition: From Current Advances to Evolving Future. Cells, 11.","DOI":"10.3390\/cells11192972"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22111","DOI":"10.1038\/s41598-021-01738-w","article-title":"Association between low density lipoprotein cholesterol and all-cause mortality: Results from the NHANES 1999\u20132014","volume":"11","author":"Liu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e023690","DOI":"10.1161\/JAHA.121.023690","article-title":"Association of Low-Density Lipoprotein Cholesterol Levels with More than 20-Year Risk of Cardiovascular and All-Cause Mortality in the General Population","volume":"11","author":"Rong","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e060172","DOI":"10.1136\/bmjopen-2021-060172","article-title":"Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: A reanalysis based on regulatory data","volume":"12","author":"Erviti","year":"2022","journal-title":"BMJ Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5245308","DOI":"10.1155\/2020\/5245308","article-title":"Mechanistic Insights into the Oxidized Low-Density Lipoprotein-Induced Atherosclerosis","volume":"2020","author":"Khatana","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1093\/eurheartj\/ehaa770","article-title":"Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1): A crucial driver of atherosclerotic cardiovascular disease","volume":"42","author":"Akhmedov","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"III2","DOI":"10.1161\/01.CIR.0000131511.50734.44","article-title":"Atherogenic lipoprotein particles in atherosclerosis","volume":"109","author":"Carmena","year":"2004","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nature01323","article-title":"Inflammation in atherosclerosis","volume":"420","author":"Libby","year":"2002","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S1050-1738(01)00111-6","article-title":"The oxidative modification hypothesis of atherosclerosis: Does it hold for humans?","volume":"11","author":"Witztum","year":"2001","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1161\/ATVBAHA.120.315421","article-title":"Role of LOX-1 (Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1) as a Cardiovascular Risk Predictor: Mechanistic Insight and Potential Clinical Use","volume":"41","author":"Barreto","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"181324","DOI":"10.1155\/2013\/181324","article-title":"Electronegative LDL: A circulating modified LDL with a role in inflammation","volume":"2013","author":"Estruch","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_21","first-page":"525","article-title":"LDL electronegativity index: A potential novel index for predicting cardiovascular disease","volume":"11","author":"Ivanova","year":"2015","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11866","DOI":"10.1038\/s41598-018-30243-w","article-title":"Range of L5 LDL levels in healthy adults and L5\u2019s predictive power in patients with hyperlipidemia or coronary artery disease","volume":"8","author":"Chu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ke, L.Y., Law, S.H., Mishra, V.K., Parveen, F., Chan, H.C., Lu, Y.H., and Chu, C.S. (2020). Molecular and Cellular Mechanisms of Electronegative Lipoproteins in Cardiovascular Diseases. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120550"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chu, C.S., Law, S.H., Lenzen, D., Tan, Y.H., Weng, S.F., Ito, E., Wu, J.C., Chen, C.H., Chan, H.C., and Ke, L.Y. (2020). Clinical Significance of Electronegative Low-Density Lipoprotein Cholesterol in Atherothrombosis. Biomedicines, 8.","DOI":"10.3390\/biomedicines8080254"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Law, S.H., Chan, M.L., Marathe, G.K., Parveen, F., Chen, C.H., and Ke, L.Y. (2019). An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051149"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1002\/art.41213","article-title":"Role of Low-Density Lipoprotein in Early Vascular Aging Associated With Systemic Lupus Erythematosus","volume":"72","author":"Chan","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jacc.2022.10.019","article-title":"Elevated LDL Triglycerides and Atherosclerotic Risk","volume":"81","author":"Balling","year":"2023","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1021\/acs.jmedchem.5b01534","article-title":"Enhanced Sphingomyelinase Activity Contributes to the Apoptotic Capacity of Electronegative Low-Density Lipoprotein","volume":"59","author":"Ke","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12967-016-0901-1","article-title":"The Apoe(-\/-) mouse model: A suitable model to study cardiovascular and respiratory diseases in the context of cigarette smoke exposure and harm reduction","volume":"14","author":"Schlage","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Petrucci, G., Rizzi, A., Hatem, D., Tosti, G., Rocca, B., and Pitocco, D. (2022). Role of Oxidative Stress in the Pathogenesis of Atherothrombotic Diseases. Antioxidants, 11.","DOI":"10.3390\/antiox11071408"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1161\/01.CIR.0000023623.87083.4F","article-title":"Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice","volume":"106","author":"Tward","year":"2002","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.3390\/cimb44100320","article-title":"Western Diet-Fed ApoE Knockout Male Mice as an Experimental Model of Non-Alcoholic Steatohepatitis","volume":"44","author":"Camargo","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.addr.2020.06.009","article-title":"\u201cLipidomics\u201d: Mass spectrometric and chemometric analyses of lipids","volume":"159","author":"Wu","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4249","DOI":"10.1021\/acs.analchem.7b05395","article-title":"Lipidomic Analysis","volume":"90","author":"Holcapek","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e32599","DOI":"10.1097\/MD.0000000000032599","article-title":"Landscape of lipidomics in cardiovascular medicine from 2012 to 2021: A systematic bibliometric analysis and literature review","volume":"101","author":"Wang","year":"2022","journal-title":"Medicine"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mir, S.A., Chen, L., Burugupalli, S., Burla, B., Ji, S., Smith, A.A.T., Narasimhan, K., Ramasamy, A., Tan, K.M., and Huynh, K. (2022). Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: A mother-offspring cohort study. BMC Med., 20.","DOI":"10.1186\/s12916-022-02432-y"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/nprot.2017.013","article-title":"Metabolomics and lipidomics using traveling-wave ion mobility mass spectrometry","volume":"12","author":"Paglia","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"497841","DOI":"10.1155\/2011\/497841","article-title":"Animal models of cardiovascular diseases","volume":"2011","author":"Zaragoza","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0092-8674(92)90362-G","article-title":"Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells","volume":"71","author":"Plump","year":"1992","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2200367","DOI":"10.1002\/mnfr.202200367","article-title":"Effect of Diets on Plasma and Aorta Lipidome: A Study in the apoE Knockout Mouse Model","volume":"67","author":"Busnelli","year":"2023","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1146\/annurev.genom.1.1.507","article-title":"Apolipoprotein E: Far more than a lipid transport protein","volume":"1","author":"Mahley","year":"2000","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"31285","DOI":"10.1074\/jbc.272.50.31285","article-title":"Heparan sulfate proteoglycans participate in hepatic lipaseand apolipoprotein E-mediated binding and uptake of plasma lipoproteins, including high density lipoproteins","volume":"272","author":"Ji","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_43","first-page":"1","article-title":"Triglyceride Metabolism in the Liver","volume":"Volume 8","author":"Cohen","year":"2017","journal-title":"Comprehensive Physiology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E1195","DOI":"10.1152\/ajpendo.90958.2008","article-title":"Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis","volume":"296","author":"Takeuchi","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/eurheartj\/ehi010","article-title":"Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease risk factors, angiographic coronary artery disease, and major adverse events at follow-up","volume":"26","author":"Brilakis","year":"2005","journal-title":"Eur. Heart J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1161\/ATVBAHA.107.142679","article-title":"Elevated Lp-PLA2 levels add prognostic information to the metabolic syndrome on incidence of cardiovascular events among middle-aged nondiabetic subjects","volume":"27","author":"Persson","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/med.21597","article-title":"Lipoprotein-associated phospholipase A2: The story continues","volume":"40","author":"Huang","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.bbalip.2013.11.013","article-title":"Micromolar changes in lysophosphatidylcholine concentration cause minor effects on mitochondrial permeability but major alterations in function","volume":"1841","author":"Hollie","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1194\/jlr.M400464-JLR200","article-title":"Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: Role of fatty acid beta-oxidation and glucose","volume":"46","author":"Vankoningsloo","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1161\/CIRCRESAHA.110.228742","article-title":"Circulating platelet-activating factor is primarily cleared by transport, not intravascular hydrolysis by lipoprotein-associated phospholipase A2\/ PAF acetylhydrolase","volume":"108","author":"Liu","year":"2011","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41574-020-0320-5","article-title":"The role of ceramides in metabolic disorders: When size and localization matters","volume":"16","author":"Bruning","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.celrep.2014.08.057","article-title":"Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance","volume":"9","author":"Contreras","year":"2014","journal-title":"Cell Rep."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Parveen, F., Bender, D., Law, S.H., Mishra, V.K., Chen, C.C., and Ke, L.Y. (2019). Role of Ceramidases in Sphingolipid Metabolism and Human Diseases. Cells, 8.","DOI":"10.3390\/cells8121573"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"14764","DOI":"10.1038\/s41598-018-33116-4","article-title":"Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients","volume":"8","author":"Gerl","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.tips.2022.06.009","article-title":"Mouse models of atherosclerosis in translational research","volume":"43","author":"Ilyas","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jnutbio.2015.11.019","article-title":"Electronegative LDL is linked to high-fat, high-cholesterol diet-induced nonalcoholic steatohepatitis in hamsters","volume":"30","author":"Lai","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/MOL.0000000000000456","article-title":"New approaches to address dyslipidemia","volume":"28","author":"Parhofer","year":"2017","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.chroma.2018.03.024","article-title":"Screening of stationary phase selectivities for global lipid profiling by ultrahigh performance supercritical fluid chromatography","volume":"1548","author":"Sandahl","year":"2018","journal-title":"J. Chromatogr. A"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nmeth.2551","article-title":"LipidBlast in silico tandem mass spectrometry database for lipid identification","volume":"10","author":"Kind","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"D1102","DOI":"10.1093\/nar\/gky1033","article-title":"PubChem 2019 update: Improved access to chemical data","volume":"47","author":"Kim","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"D456","DOI":"10.1093\/nar\/gks1146","article-title":"The ChEBI reference database and ontology for biologically relevant chemistry: Enhancements for 2013","volume":"41","author":"Hastings","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"eaaw2964","DOI":"10.1126\/scisignal.aaw2964","article-title":"LIPID MAPS: Serving the next generation of lipid researchers with tools, resources, data, and training","volume":"12","author":"Dennis","year":"2019","journal-title":"Sci. Signal."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/6956\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:12:43Z","timestamp":1760123563000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/6956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,9]]},"references-count":65,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24086956"],"URL":"https:\/\/doi.org\/10.3390\/ijms24086956","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,9]]}}}