{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:54Z","timestamp":1787028954025,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Ceramides are a family of lipid molecules, composed of sphingosine and a fatty acid, and transported by lipoproteins (primarily by low-density lipoproteins) in the bloodstream. They are not only structural lipids, but multifunctional and bioactive molecules with key roles in many important cellular pathways, such as inflammatory processes and apoptosis, representing potential biomarkers of cardiometabolic diseases as well as pharmacological targets. Recent data reported ceramide modulation by diet and aerobic exercise, suggesting nutrients and exercise-targeting sphingolipid pathways as a countermeasure, also in combination with other therapies, for risk and progression of chronic disease prevention and health maintenance. In this review, we focus on the available data regarding remarks on ceramide structure and metabolism, their pathophysiologic roles, and the effect of dietary habit and aerobic exercise on ceramide levels. Moreover, advancements and limitations of lipidomic techniques and simplification attempts to overcome difficulties of interpretation and to facilitate practical applications, such as the proposal of scores, are also discussed.<\/jats:p>","DOI":"10.3390\/metabo11110719","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:22:02Z","timestamp":1634862122000},"page":"719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Plasma Ceramides Pathophysiology, Measurements, Challenges, and Opportunities"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6311-502X","authenticated-orcid":false,"given":"Melania","family":"Gaggini","sequence":"first","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-184X","authenticated-orcid":false,"given":"Alessandro","family":"Pingitore","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3438-6450","authenticated-orcid":false,"given":"Cristina","family":"Vassalle","sequence":"additional","affiliation":[{"name":"Fondazione CNR-Regione Toscana G. Monasterio, Via Moruzzi, 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and their metabolism in physiology and disease","volume":"19","author":"Hannun","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41569-021-00536-1","article-title":"Ceramides and other sphingolipids as drivers of cardiovascular disease","volume":"18","author":"Choi","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yun, H., Sun, L., Wu, Q., Zong, G., Qi, Q., Li, H., Zheng, H., Zeng, R., Liang, L., and Lin, X. (2020). Associations among circulating sphingolipids, \u03b2-cell function, and risk of developing type 2 diabetes: A population-based cohort study in China. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003451"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ayub, M., Jin, H.K., and Bae, J.S. (2021). Novelty of sphingolipids in the central nervous system physiology and disease: Focusing on the sphingolipid hypothesis of neuroinflammation and neurodegeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147353"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Piazzesi, A., Afsar, S.Y., and van Echten-Deckert, G. (2021). Sphingolipid metabolism in the development and progression of cancer: One cancer\u2019s help is another\u2019s hindrance. Mol. Oncol.","DOI":"10.1002\/1878-0261.13063"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Custodia, A., Aramburu-N\u00fa\u00f1ez, M., Correa-Paz, C., Posado-Fern\u00e1ndez, A., G\u00f3mez-Larrauri, A., Castillo, J., G\u00f3mez-Mu\u00f1oz, A., Sobrino, T., and Ouro, A. (2021). Ceramide metabolism and parkinson\u2019s disease\u2014Therapeutic targets. Biomolecules, 11.","DOI":"10.3390\/biom11070945"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"717","DOI":"10.3233\/JAD-181203","article-title":"Plasma Sphingolipids Mediate a Relationship between Type 2 Diabetes and Memory Outcomes in Patients with Coronary Artery Disease Undertaking Exercise","volume":"69","author":"Eakin","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7249","DOI":"10.1038\/s41598-018-25397-6","article-title":"The effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action","volume":"8","author":"Zabielski","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1530\/JOE-16-0381","article-title":"Effect of metformin on bioactive lipid metabolism in insulin-resistant muscle","volume":"233","author":"Zabielski","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1161\/CIRCULATIONAHA.116.024261","article-title":"Plasma ceramides, mediterranean diet, and incident cardiovascular disease in the PREDIMED trial (prevenci\u00f3n con dieta mediterr\u00e1nea)","volume":"135","author":"Wang","year":"2017","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1093\/jn\/nxaa269","article-title":"Dietary patterns, ceramide ratios, and risk of all-cause and cause-specific mortality: The framingham offspring study","volume":"150","author":"Walker","year":"2020","journal-title":"J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1249\/MSS.0000000000002030","article-title":"One-Year Lifestyle Intervention, Muscle Lipids, and Cardiometabolic Risk","volume":"51","author":"Maltais","year":"2019","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1080\/13697137.2018.1526892","article-title":"Effects of concurrent exercise on cardiometabolic status during perimenopause: The FLAMENCO Project","volume":"21","author":"Aranda","year":"2018","journal-title":"Climacteric"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wun, C.H., Zhang, M.J., Ho, B.H., McGeough, K., Tan, F., and Aziz, A.R. (2020). Efficacy of a six-week dispersed wingate-cycle training protocol on peak aerobic power, leg strength, insulin sensitivity, blood lipids and quality of life in healthy adults. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17134860"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2144\/btn-2019-0138","article-title":"Conventional and innovative methods to assess oxidativestressbiomarkersintheclinicalcardiovascular setting","volume":"68","author":"Gaggini","year":"2020","journal-title":"Biotechniques"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Reidy, P.T., Mahmassani, Z.S., McKenzie, A.I., Petrocelli, J.J., Summers, S.A., and Drummond, M.J. (2020). Influence of exercise training on skeletal muscle insulin resistance in aging: Spotlight on muscle ceramides. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041514"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gaggini, M., Vassalle, C., Carli, F., Maltinti, M., Sabatino, L., Buzzigoli, E., Mastorci, F., Sbrana, F., Gastaldelli, A., and Pingitore, A. (2021). Changes in plasma bioactive lipids and inflammatory markers during a half-marathon in trained athletes. Appl. Sci., 11.","DOI":"10.3390\/app11104622"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1002\/oby.21117","article-title":"Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes","volume":"23","author":"Kasumov","year":"2015","journal-title":"Obesity"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"570628","DOI":"10.3389\/fendo.2020.570628","article-title":"Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification","volume":"11","author":"Hilvo","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1021\/acs.jmedchem.0c01664","article-title":"Small Molecule Inhibitors Targeting Biosynthesis of Ceramide, the Central Hub of the Sphingolipid Network","volume":"64","author":"Slusher","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrc3398","article-title":"Ceramide-orchestrated signalling in cancer cells","volume":"13","author":"Morad","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Raichur, S. (2020). Ceramide Synthases Are Attractive Drug Targets for Treating Metabolic Diseases. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00483"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1172\/JCI0216390","article-title":"Cholesterol, lipid rafts, and disease","volume":"110","author":"Simons","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1016\/j.bpj.2021.06.009","article-title":"Identification of a critical lipid ratio in raft-like phases exposed to nitric oxide: An AFM study","volume":"120","author":"Karanth","year":"2021","journal-title":"Biophys. J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ladjohounlou, R., Louati, S., Lauret, A., Gauthier, A., Ardail, D., Magne, N., Alphonse, G., and Rodriguez-Lafrasse, C. (2020). Ceramide-enriched membrane domains contribute to targeted and nontargeted effects of radiation through modulation of pi3k\/akt signaling in hnscc cells. Int. J. Mol. Sci., 21.","DOI":"10.2139\/ssrn.3571515"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1084\/jem.20041685","article-title":"Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis","volume":"202","author":"Miyaji","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"27596","DOI":"10.18632\/oncotarget.4820","article-title":"By activating Fas\/ceramide synthase 6\/p38 kinase in lipid rafts, Stichoposide D inhibits growth of leukemia xenografts","volume":"6","author":"Yun","year":"2015","journal-title":"Oncotarget"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/bs.vh.2017.02.002","article-title":"Erythropoietin Receptor Signaling and Lipid Rafts","volume":"105","author":"McGraw","year":"2017","journal-title":"Vitam. Horm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.freeradbiomed.2021.02.016","article-title":"The role of ceramide accumulation in human induced pluripotent stem cell-derived cardiomyocytes on mitochondrial oxidative stress and mitophagy","volume":"167","author":"Bekhite","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.bbadis.2018.11.011","article-title":"Neuronal ceroid lipofuscinosis related ER membrane protein CLN8 regulates PP2A activity and ceramide levels","volume":"1865","author":"Adhikari","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"83907","DOI":"10.18632\/oncotarget.13438","article-title":"Ceramide activates lysosomal cathepsin B and cathepsin D to attenuate autophagy and induces ER stress to suppress myeloidderived suppressor cells","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/978-3-7091-1368-4_6","article-title":"Membrane channels formed by ceramide","volume":"215","author":"Colombini","year":"2013","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cmet.2021.06.006","article-title":"Sphingolipids in metabolic disease: The good, the bad, and the unknown","volume":"33","author":"Green","year":"2021","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"\u0160r\u00e1mek, J., N\u011bmcov\u00e1-f\u00fcrstov\u00e1, V., and Kov\u00e1\u0159, J. (2021). Molecular mechanisms of apoptosis induction and its regulation by fatty acids in pancreatic \u03b2-cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084285"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.bbamem.2014.11.018","article-title":"Very long chain ceramides interfere with C16-ceramide-induced channel formation: A plausible mechanism for regulating the initiation of intrinsic apoptosis","volume":"1848","author":"Stiban","year":"2015","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.biocel.2013.03.012","article-title":"The equilibrium between long and very long chain ceramides is important for the fate of the cell and can be influenced by co-expression of CerS","volume":"45","author":"Hartmann","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1517\/14728222.2011.588209","article-title":"Ceramide formation as a target in beta-cell survival and function","volume":"15","author":"Lang","year":"2011","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1007\/s00395-011-0223-7","article-title":"A novel role for mitochondrial sphingosine-1-phosphate produced by sphingosine kinase-2 in PTP-mediated cell survival during cardioprotection","volume":"106","author":"Gomez","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"H3150","DOI":"10.1152\/ajpheart.00587.2006","article-title":"Signals from type 1 sphingosine 1-phosphate receptors enhance adult mouse cardiac myocyte survival during hypoxia","volume":"293","author":"Zhang","year":"2007","journal-title":"Am. J. Physiol. Hear. Circ. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.molmed.2018.10.009","article-title":"Ceramides as Novel Disease Biomarkers","volume":"25","author":"Kurz","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15371","DOI":"10.1074\/jbc.R115.653204","article-title":"Dihydroceramides: From bit players to lead actors","volume":"290","author":"Siddique","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1080\/15548627.2020.1761651","article-title":"The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells","volume":"17","author":"Casas","year":"2021","journal-title":"Autophagy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.atherosclerosis.2021.04.021","article-title":"Circulating ceramides as biomarkers of cardiovascular disease: Evidence from phenotypic and genomic studies","volume":"327","author":"McGurk","year":"2021","journal-title":"Atherosclerosis"},{"key":"ref_44","first-page":"143","article-title":"Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes","volume":"12","author":"Zabielski","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ismaeel, A., Franco, M.E., Lavado, R., Papoutsi, E., Casale, G.P., Fuglestad, M., Mietus, C.J., Haynatzki, G.R., Smith, R.S., and Bohannon, W.T. (2019). Altered metabolomic profile in patients with peripheral artery disease. J. Clin. Med., 8.","DOI":"10.3390\/jcm8091463"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E398","DOI":"10.1152\/ajpendo.00134.2015","article-title":"Serum sphingolipids: Relationships to insulin sensitivity and changes with exercise in humans","volume":"309","author":"Bergman","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"662","DOI":"10.3945\/jn.115.220459","article-title":"A healthy Nordic diet alters the plasma lipidomic profile in adults with features of metabolic syndrome in a multicenter randomized dietary intervention","volume":"146","author":"Lankinen","year":"2016","journal-title":"J. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.1749-6632.2002.tb04279.x","article-title":"The sphingomyelin-signaling pathway in skeletal muscles and its role in regulation of glucose uptake","volume":"967","author":"Dobrzyn","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s00125-011-2065-0","article-title":"Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide","volume":"54","author":"Amati","year":"2011","journal-title":"Diabetologia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1038\/ijo.2017.170","article-title":"Lipid droplet remodelling and reduced muscle ceramides following sprint interval and moderate-intensity continuous exercise training in obese males","volume":"41","author":"Shepherd","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1161\/CIRCRESAHA.116.308999","article-title":"Obesity, diabetes, and cardiovascular diseases","volume":"118","author":"Scherer","year":"2016","journal-title":"Circ. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"401","DOI":"10.2337\/db12-0686","article-title":"Ceramides Contained in LDL Are Elevated in Type 2 Diabetes and Promote Inflammation and Skeletal Muscle Insulin Resistance","volume":"62","author":"Boon","year":"2013","journal-title":"Diabetes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10297","DOI":"10.1074\/jbc.M212307200","article-title":"A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids","volume":"278","author":"Chavez","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1748-1716.2007.01755.x","article-title":"Effect of exercise duration on ceramide metabolism in the rat heart","volume":"192","author":"Baranowski","year":"2008","journal-title":"Acta Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/jcb.21877","article-title":"Effect of exercise duration on the key pathways of ceramide metabolism in rat skeletal muscles","volume":"105","author":"Baranowski","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1748-1716.2011.02322.x","article-title":"Exercise increases plasma levels of sphingoid base-1 phosphates in humans","volume":"203","author":"Baranowski","year":"2011","journal-title":"Acta Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1123\/ijsnem.2013-0093","article-title":"Ultramarathon run markedly reduces plasma sphingosine-1-phosphate concentration","volume":"24","author":"Baranowski","year":"2014","journal-title":"Int. J. Sport Nutr. Exerc. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s00421-014-3080-x","article-title":"Exercise increases sphingoid base-1-phosphate levels in human blood and skeletal muscle in a time- and intensity-dependent manner","volume":"115","author":"Baranowski","year":"2015","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"S\u00f8gaard, D., Baranowski, M., Larsen, S., Lund, M.T., Scheuer, C.M., Abildskov, C.V., Dideriksen, S.G., Dela, F., and Helge, J.W. (2019). Muscle-saturated bioactive lipids are increased with aging and influenced by high-intensity interval training. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051240"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4536470","DOI":"10.1155\/2016\/4536470","article-title":"Endurance and resistance training affect high fat diet-induced increase of ceramides, inflammasome expression, and systemic inflammation in mice","volume":"2016","author":"Mardare","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Mietus-Snyder, M., Narayanan, N., Krauss, R.M., Laine-Graves, K., McCann, J.C., Shigenaga, M.K., McHugh, T.H., Ames, B.N., and Suh, J.H. (2020). Randomized nutrient bar supplementation improves exercise-associated changes in plasma metabolome in adolescents and adult family members at cardiometabolic risk. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240437"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.plipres.2019.04.001","article-title":"Ceramide and sphingosine 1-phosphate in adipose dysfunction","volume":"74","author":"Fang","year":"2019","journal-title":"Prog. Lipid Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1042\/CS20180409","article-title":"Amino acid and lipid associated plasma metabolomic patterns are related to healthspan indicators with ageing","volume":"132","author":"Johnson","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1038\/s41598-020-59051-x","article-title":"Plasma lipid profile associates with the improvement of psychological well-being in individuals with perceived stress symptoms","volume":"10","author":"Noerman","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13139","DOI":"10.1038\/s41598-021-92576-3","article-title":"Association between serum sphingolipids and eudaimonic well-being in white U.S. adults","volume":"11","author":"Berkowitz","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.cmet.2014.08.002","article-title":"Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance","volume":"20","author":"Turpin","year":"2014","journal-title":"Cell Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.cmet.2014.09.015","article-title":"CerS2 haploinsufficiency inhibits \u03b2-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance","volume":"20","author":"Raichur","year":"2014","journal-title":"Cell Metab."},{"key":"ref_68","first-page":"5","article-title":"LC-MS\/MS in the clinical laboratory\u2014Where to from here?","volume":"32","author":"Grebe","year":"2011","journal-title":"Clin. Biochem. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1093\/eurheartj\/ehw148","article-title":"Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol","volume":"37","author":"Laaksonen","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1161\/ATVBAHA.116.307497","article-title":"Circulating Ceramides Predict Cardiovascular Outcomes in the Population-Based FINRISK 2002 Cohort","volume":"36","author":"Havulinna","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/eurheartj\/ehz387","article-title":"Development and validation of a ceramide-and phospholipid-based cardiovascular risk estimation score for coronary artery disease patients","volume":"41","author":"Hilvo","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e015258","DOI":"10.1161\/JAHA.119.015258","article-title":"Prediction of residual risk by ceramide-phospholipid score in patients with stable coronary heart disease on optimal medical therapy","volume":"9","author":"Hilvo","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1007\/s00125-018-4590-6","article-title":"Ceramide stearic to palmitic acid ratio predicts incident diabetes","volume":"61","author":"Hilvo","year":"2018","journal-title":"Diabetologia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1172\/JCI131838","article-title":"Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease","volume":"130","author":"Poss","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jacc.2020.11.030","article-title":"Machine Learning and the Future of Cardiovascular Care: JACC State-of-the-Art Review","volume":"77","author":"Quer","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1093\/gerona\/glaa072","article-title":"Le Ceramide Biomarkers Predictive of Cardiovascular Disease Risk Increase in Healthy Older Adults after Bed Rest","volume":"75","author":"Petrocelli","year":"2020","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1093\/eurheartj\/ehx205","article-title":"Plasma ceramides and cardiac risk","volume":"38","author":"Nicholls","year":"2017","journal-title":"Eur. 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