{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:57:56Z","timestamp":1790859476150,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) has been consistently linked to increased risk of cardiovascular disease (CVD). HDL lipoproteins may serve as a possible link in this association through their hepatic synthesis and atheroprotective properties. Serum samples were collected from 51 MASLD patients (diagnosed by abdominal ultrasound), 40 with coronary artery disease, and 50 healthy controls. HDL lipid profiles were investigated by proton nuclear magnetic resonance (1H NMR) spectroscopy. Patients with MASLD exhibit an increased percentage of lysophosphatidylcholine and sphingolipid content, mainly due to increased ceramides, and a reduced percentage of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol compared to controls. The % content of total and individual polyunsaturated fatty acids including linoleic, docosahexaenoic, eicosapentaenoic, and arachidonic acid was found to be reduced in patients with MASLD, while saturated fatty acid content was increased compared to the control group. These alterations in fatty acid composition were observed also in CAD patients compared to controls but were more pronounced in CAD patients. Compared to CAD patients, those with MASLD showed an increased content of sphingolipids, ceramides, and glycerolipids and a reduced content of phosphatidylinositol. Changes observed in the lipid composition of HDL lipoproteins in MASLD patients may impair the protective properties of HDL particles, contributing to increased CVD risk.<\/jats:p>","DOI":"10.3390\/ijms26136148","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T06:55:13Z","timestamp":1750920913000},"page":"6148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Altered HDL Phospholipid and Fatty Acid Profile in MASLD: A Possible Explanation for the Increased CVD Risk"],"prefix":"10.3390","volume":"26","author":[{"given":"Sofia","family":"Kartsoli","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, School of Health Sciences, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7045-1323","authenticated-orcid":false,"given":"Christina E.","family":"Kostara","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry, School of Health Sciences, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Papathanasiou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Health Sciences, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1708-3415","authenticated-orcid":false,"given":"Vasilis","family":"Tsimihodimos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Health Sciences, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni T.","family":"Bairaktari","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry, School of Health Sciences, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9694-1160","authenticated-orcid":false,"given":"Dimitrios K.","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, School of Health Sciences, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.3350\/cmh.2024.0431","article-title":"Epidemiology of Metabolic Dysfunction-Associated Steatotic Liver Disease","volume":"31","author":"Younossi","year":"2024","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_2","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) (2024). EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). J. Hepatol., 81, 492\u2013542."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrendo.2016.169","article-title":"Sphingolipids and Phospholipids in Insulin Resistance and Related Metabolic Disorders","volume":"13","author":"Meikle","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jhep.2016.05.013","article-title":"Non-Alcoholic Fatty Liver Disease and Risk of Incident Cardiovascular Disease: A Meta-Analysis","volume":"65","author":"Targher","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"492","DOI":"10.2459\/JCM.0000000000001488","article-title":"Cardiovascular Prevention in Childhood: A Consensus Document of the Italian Society of Cardiology Working Group on Congenital Heart Disease and Cardiovascular Prevention in Paediatric Age","volume":"24","author":"Martino","year":"2023","journal-title":"J. Cardiovasc. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1194\/jlr.R039297","article-title":"Cardioprotective Functions of HDLs","volume":"55","author":"Rye","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"52","DOI":"10.5551\/jat.E571","article-title":"Antiatherogenic Functionality of High Density Lipoprotein: How Much versus How Gooden-Subtitle=","volume":"15","author":"Sviridov","year":"2008","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2005.08.008","article-title":"Structural Modifications of HDL and Functional Consequences","volume":"184","author":"Ferretti","year":"2006","journal-title":"Atherosclerosis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.atherosclerosis.2012.02.032","article-title":"Inflammation Modulates Human HDL Composition and Function in Vivo","volume":"222","author":"McGillicuddy","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101728","DOI":"10.1016\/j.molmet.2023.101728","article-title":"Non-Alcoholic Fatty Liver Disease Is Characterised by a Reduced Polyunsaturated Fatty Acid Transport via Free Fatty Acids and High-Density Lipoproteins (HDL)","volume":"73","author":"Mocciaro","year":"2023","journal-title":"Mol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1194\/jlr.R300004-JLR200","article-title":"Global Analyses of Cellular Lipidomes Directly from Crude Extracts of Biological Samples by ESI Mass Spectrometry: A Bridge to Lipidomics","volume":"44","author":"Han","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.tibtech.2008.09.001","article-title":"Lipidomics: A New Window to Biomedical Frontiers","volume":"26","author":"Oresic","year":"2008","journal-title":"Trends Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.plipres.2017.09.003","article-title":"Applications of Nuclear Magnetic Resonance in Lipid Analyses: An Emerging Powerful Tool for Lipidomics Studies","volume":"68","author":"Li","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/hep.21763","article-title":"A Lipidomic Analysis of Nonalcoholic Fatty Liver Disease","volume":"46","author":"Puri","year":"2007","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wattacheril, J., Seeley, E.H., Angel, P., Chen, H., Bowen, B.P., Lanciault, C., Caprioli, R.M., Abumrad, N., and Flynn, C.R. (2013). Differential Intrahepatic Phospholipid Zonation in Simple Steatosis and Nonalcoholic Steatohepatitis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057165"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chiappini, F., Coilly, A., Kadar, H., Gual, P., Tran, A., Desterke, C., Samuel, D., Duclos-Vall\u00e9e, J.-C., Touboul, D., and Bertrand-Michel, J. (2017). Metabolism Dysregulation Induces a Specific Lipid Signature of Nonalcoholic Steatohepatitis in Patients. Sci. Rep., 7.","DOI":"10.1038\/srep46658"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41575-024-01020-0","article-title":"High-Density Lipoprotein Lipidome: A Neglected Source of Hepatic Lipids","volume":"22","author":"Mocciaro","year":"2025","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1161\/CIRCULATIONAHA.106.621433","article-title":"Both Hepatic and Extrahepatic ABCA1 Have Discrete and Essential Functions in the Maintenance of Plasma High-Density Lipoprotein Cholesterol Levels in Vivo","volume":"114","author":"Singaraja","year":"2006","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.bbalip.2011.09.009","article-title":"Phosphatidylcholine Biosynthesis and Lipoprotein Metabolism","volume":"1821","author":"Cole","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.cell.2011.09.045","article-title":"A Conserved SREBP-1\/Phosphatidylcholine Feedback Circuit Regulates Lipogenesis in Metazoans","volume":"147","author":"Walker","year":"2011","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.bbamem.2017.04.006","article-title":"The Critical Role of Phosphatidylcholine and Phosphatidylethanolamine Metabolism in Health and Disease","volume":"1859","author":"Kennelly","year":"2017","journal-title":"Biochim. Biophys. Acta BBA Biomembr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"436","DOI":"10.4254\/wjh.v12.i8.436","article-title":"Lipidomics in Non-Alcoholic Fatty Liver Disease","volume":"12","author":"Kartsoli","year":"2020","journal-title":"World J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Shama, S., Jang, H., Wang, X., Zhang, Y., Shahin, N.N., Motawi, T.K., Kim, S., Gawrieh, S., and Liu, W. (2023). Phosphatidylethanolamines Are Associated with Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Adults and Induce Liver Cell Metabolic Perturbations and Hepatic Stellate Cell Activation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021034"},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"e12988","DOI":"10.1111\/eci.12988","article-title":"Plasma Lecithin:Cholesterol Acyltransferase and Phospholipid Transfer Protein Activity Independently Associate with Nonalcoholic Fatty Liver Disease","volume":"48","author":"Nass","year":"2018","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1089\/met.2011.0111","article-title":"Association of Serum Lipoprotein-Associated Phospholipase A2 Level with Nonalcoholic Fatty Liver Disease","volume":"10","author":"Colak","year":"2012","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gorden, D.L., Ivanova, P.T., Myers, D.S., McIntyre, J.O., VanSaun, M.N., Wright, J.K., Matrisian, L.M., and Brown, H.A. (2011). Increased Diacylglycerols Characterize Hepatic Lipid Changes in Progression of Human Nonalcoholic Fatty Liver Disease; Comparison to a Murine Model. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022775"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.tem.2012.04.005","article-title":"Role of Ceramides in Nonalcoholic Fatty Liver Disease","volume":"23","author":"Pagadala","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1194\/jlr.R036095","article-title":"Unraveling the Complexities of the HDL Lipidome1","volume":"54","author":"Kontush","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/S0022-2275(20)31997-0","article-title":"Influence of Phospholipid Depletion on the Size, Structure, and Remodeling of Reconstituted High Density Lipoproteins","volume":"41","author":"Rye","year":"2000","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"36596","DOI":"10.1074\/jbc.M006924200","article-title":"High Density Lipoprotein Phospholipid Composition Is a Major Determinant of the Bi-Directional Flux and Net Movement of Cellular Free Cholesterol Mediated by Scavenger Receptor BI","volume":"275","author":"Yancey","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.bbalip.2015.05.007","article-title":"Defective Functionality of Small, Dense HDL3 Subpopulations in ST Segment Elevation Myocardial Infarction: Relevance of Enrichment in Lysophosphatidylcholine, Phosphatidic Acid and Serum Amyloid A","volume":"1851","author":"Rached","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fadaei, R., Poustchi, H., Meshkani, R., Moradi, N., Golmohammadi, T., and Merat, S. (2018). Impaired HDL Cholesterol Efflux Capacity in Patients with Non-Alcoholic Fatty Liver Disease Is Associated with Subclinical Atherosclerosis. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-29639-5"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S0022-2275(20)33434-9","article-title":"Phospholipid Composition of Reconstituted High Density Lipoproteins Influences Their Ability to Inhibit Endothelial Cell Adhesion Molecule Expression","volume":"41","author":"Baker","year":"2000","journal-title":"J. Lipid Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/S0022-2275(20)33428-3","article-title":"Phosphatidylinositol Promotes Cholesterol Transport in Vivo","volume":"41","author":"Stamler","year":"2000","journal-title":"J. Lipid Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.metabol.2016.01.011","article-title":"Fatty Acid Metabolism Is Altered in Non-Alcoholic Steatohepatitis Independent of Obesity","volume":"65","author":"Walle","year":"2016","journal-title":"Metabolism"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1053\/j.gastro.2018.06.031","article-title":"Bioactive Lipid Species and Metabolic Pathways in Progression and Resolution of Nonalcoholic Steatohepatitis","volume":"155","author":"Musso","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_38","first-page":"72","article-title":"Analysis of the Composition of Plasma Lipoproteins in Patients with Extensive Coronary Heart Disease Using 1H NMR Spectroscopy","volume":"49","author":"Papathanasiou","year":"2008","journal-title":"Hell. J. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1021\/pr500061n","article-title":"NMR-Based Lipidomic Analysis of Blood Lipoproteins Differentiates the Progression of Coronary Heart Disease","volume":"13","author":"Kostara","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1021\/pr900783x","article-title":"Evaluation of Established Coronary Heart Disease on the Basis of HDL and Non-HDL NMR Lipid Profiling","volume":"9","author":"Kostara","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_41","first-page":"129","article-title":"The Functional and Compositional Properties of Lipoproteins Are Altered in Patients with Metabolic Syndrome with Increased Cholesteryl Ester Transfer Protein Activity","volume":"25","author":"Park","year":"2010","journal-title":"Int. J. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4963","DOI":"10.1210\/jc.2004-0305","article-title":"Metabolic Syndrome Is Associated with Elevated Oxidative Stress and Dysfunctional Dense High-Density Lipoprotein Particles Displaying Impaired Antioxidative Activity","volume":"89","author":"Hansel","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kostara, C.E., Ferrannini, E., Bairaktari, E.T., Papathanasiou, A., Elisaf, M., and Tsimihodimos, V. (2020). Early Signs of Atherogenic Features in the HDL Lipidomes of Normolipidemic Patients Newly Diagnosed with Type 2 Diabetes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228835"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S1050-1738(01)00084-6","article-title":"Mechanisms of Hepatic Very Low-Density Lipoprotein Overproduction in Insulin Resistance","volume":"11","author":"Adeli","year":"2001","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5712","DOI":"10.1021\/bi992902m","article-title":"The Conformation of Apolipoprotein A-I in High-Density Lipoproteins Is Influenced by Core Lipid Composition and Particle Size:\u2009 A Surface Plasmon Resonance Study","volume":"39","author":"Curtiss","year":"2000","journal-title":"Biochemistry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1172\/JCI5286","article-title":"Triglyceride Enrichment of HDL Enhances in Vivo Metabolic Clearance of HDL Apo A-I in Healthy Men","volume":"103","author":"Lamarche","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1194\/jlr.M100431-JLR200","article-title":"LDL and HDL Enriched in Triglyceride Promote Abnormal Cholesterol Transport","volume":"43","author":"Skeggs","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4804","DOI":"10.1074\/jbc.M008725200","article-title":"Elevated Triglyceride Content Diminishes the Capacity of High Density Lipoprotein to Deliver Cholesteryl Esters via the Scavenger Receptor Class B Type I (SR-BI)","volume":"276","author":"Greene","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_49","first-page":"370","article-title":"Physical Signs and Atherosclerotic Cardiovascular Disease in Familial Hypercholesterolemia: The HELLAS-FH Registry","volume":"25","author":"Rallidis","year":"2024","journal-title":"J. Cardiovasc. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1093\/eurheartj\/ehv320","article-title":"2015 ESC Guidelines for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)","volume":"37","author":"Roffi","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_51","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_52","doi-asserted-by":"crossref","unstructured":"Lutz, N.W., Sweedler, J.V., and Wevers, R.A. (2013). Lipid Profiling in Health and Disease. Methodologies for Metabolomics: Experimental Strategies and Techniques, Cambridge University Press.","DOI":"10.1017\/CBO9780511996634"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6148\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:59:09Z","timestamp":1760032749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,26]]},"references-count":52,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26136148"],"URL":"https:\/\/doi.org\/10.3390\/ijms26136148","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,26]]}}}