{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:48Z","timestamp":1787028948657,"version":"build-2736575974"},"reference-count":107,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"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>Cardiometabolic diseases (CMD) represent a growing socioeconomic burden and concern for healthcare systems worldwide. Improving patients\u2019 metabolic phenotyping in clinical practice will enable clinicians to better tailor prevention and treatment strategy to individual needs. Recently, elevated levels of specific lipid species, known as ceramides, were shown to predict cardiometabolic outcomes beyond traditional biomarkers such as cholesterol. Preliminary data showed that physical activity, a potent, low-cost, and patient-empowering means to reduce CMD-related burden, influences ceramide levels. While a single bout of physical exercise increases circulating and muscular ceramide levels, regular exercise reduces ceramide content. Additionally, several ceramide species have been reported to be negatively associated with cardiorespiratory fitness, which is a potent health marker reflecting training level. Thus, regular exercise could optimize cardiometabolic health, partly by reversing altered ceramide profiles. This short review provides an overview of ceramide metabolism and its role in cardiometabolic health and diseases, before presenting the effects of exercise on ceramides in humans.<\/jats:p>","DOI":"10.3390\/metabo11100675","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:57:54Z","timestamp":1633917474000},"page":"675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["How Ceramides Orchestrate Cardiometabolic Health\u2014An Ode to Physically Active Living"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2380-105X","authenticated-orcid":false,"given":"Justin","family":"Carrard","sequence":"first","affiliation":[{"name":"Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, University of Basel, Birsstrasse 320B, 4052 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2333-0646","authenticated-orcid":false,"given":"Hector","family":"Gallart-Ayala","sequence":"additional","affiliation":[{"name":"Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, Quartier UNIL-CHUV, Rue du Bugnon 19, 1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Weber","sequence":"additional","affiliation":[{"name":"Medical School, Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Universit\u00e4tstrasse 2, 8092 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Colledge","sequence":"additional","affiliation":[{"name":"Division of Sports Science, Department of Sport, Exercise and Health, University of Basel, Birsstrasse 320B, 4052 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-8610","authenticated-orcid":false,"given":"Lukas","family":"Streese","sequence":"additional","affiliation":[{"name":"Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, University of Basel, Birsstrasse 320B, 4052 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henner","family":"Hanssen","sequence":"additional","affiliation":[{"name":"Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, University of Basel, Birsstrasse 320B, 4052 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schmied","sequence":"additional","affiliation":[{"name":"Sports Cardiology Section, Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8267-2705","authenticated-orcid":false,"given":"Julijana","family":"Ivanisevic","sequence":"additional","affiliation":[{"name":"Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, Quartier UNIL-CHUV, Rue du Bugnon 19, 1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno","family":"Schmidt-Trucks\u00e4ss","sequence":"additional","affiliation":[{"name":"Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, University of Basel, Birsstrasse 320B, 4052 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the global burden of disease study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Murray, C.J.B.R., Foreman, K.J., and GBD 2019 DALYs and HALE Collaborator (2019). Global, regional, and national disability-adjusted life years (dalys) for diseases and injuries and healthy life expectancy (hale), 1990 to 2019: Quantifying the epidemiological transition. GBD Compare Data Visualization, Institute for Health Metrics and Evaluation, University of Washington."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1056\/NEJMra1109345","article-title":"Noncommunicable diseases","volume":"369","author":"Hunter","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"(2015). Global, regional, and national age\u2013sex specific all-cause and cause-specific mortality for 240 causes of death, 1990\u20132013: A systematic analysis for the global burden of disease study 2013. Lancet, 385, 117\u2013171.","DOI":"10.1016\/S0140-6736(14)61682-2"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.gheart.2016.10.024","article-title":"The global burden of disease study and the preventable burden of ncd","volume":"11","author":"Benziger","year":"2016","journal-title":"Glob. Heart"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/0002-9343(48)90447-1","article-title":"Cholesterol metabolism and its relationship to atherosclerosis, coronary artery disease, and arteriosclerosis","volume":"4","author":"Morrison","year":"1948","journal-title":"Am. J. Med."},{"key":"ref_7","first-page":"1","article-title":"History in medicine: The story of cholesterol, lipids and cardiology","volume":"19","author":"Kuijpers","year":"2021","journal-title":"J. Cradiol. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.plipres.2015.12.002","article-title":"Novel advances in shotgun lipidomics for biology and medicine","volume":"61","author":"Wang","year":"2016","journal-title":"Prog. Lipid Res."},{"key":"ref_9","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_10","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_11","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1161\/ATVBAHA.118.311199","article-title":"Plasma ceramides","volume":"38","author":"Meeusen","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_12","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":"2019","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.cmet.2017.12.003","article-title":"Could ceramides become the new cholesterol?","volume":"27","author":"Summers","year":"2018","journal-title":"Cell Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1136\/bjsports-2020-102955","article-title":"World health organization 2020 guidelines on physical activity and sedentary behaviour","volume":"54","author":"Bull","year":"2020","journal-title":"Br. J. Sports Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0140-6736(12)60865-4","article-title":"Sport and exercise as contributors to the health of nations","volume":"380","author":"Khan","year":"2012","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S0140-6736(12)60898-8","article-title":"The pandemic of physical inactivity: Global action for public health","volume":"380","author":"Kohl","year":"2012","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0140-6736(12)61031-9","article-title":"Effect of physical inactivity on major non-communicable diseases worldwide: An analysis of burden of disease and life expectancy","volume":"380","author":"Lee","year":"2012","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/eurheartj\/ehaa605","article-title":"2020 esc guidelines on sports cardiology and exercise in patients with cardiovascular disease","volume":"42","author":"Pelliccia","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41569-018-0065-1","article-title":"Exercise benefits in cardiovascular disease: Beyond attenuation of traditional risk factors","volume":"15","author":"Joyner","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1161\/CIRCRESAHA.118.312669","article-title":"Sedentary behavior, exercise, and cardiovascular health","volume":"124","author":"Lavie","year":"2019","journal-title":"Circ. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/sms.12581","article-title":"Exercise as medicine\u2014Evidence for prescribing exercise as therapy in 26 different chronic diseases","volume":"25","author":"Pedersen","year":"2015","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/eurheartj\/ehz486","article-title":"2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)","volume":"41","author":"Cosentino","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41574-020-0381-5","article-title":"Diet and exercise in the prevention and treatment of type 2 diabetes mellitus","volume":"16","author":"Magkos","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1007\/s00125-016-4051-z","article-title":"Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: A randomised controlled trial","volume":"59","author":"Slentz","year":"2016","journal-title":"Diabetologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1080\/17461391.2019.1571114","article-title":"Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (nafld): Roles of oxidative stress and inflammation","volume":"19","author":"Farzanegi","year":"2019","journal-title":"Eur. J. Sport Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1016\/S0140-6736(17)31634-3","article-title":"The effect of physical activity on mortality and cardiovascular disease in 130,000 people from 17 high-income, middle-income, and low-income countries: The pure study","volume":"390","author":"Lear","year":"2017","journal-title":"Lancet"},{"key":"ref_27","first-page":"126","article-title":"Physical activity, exercise, and physical fitness: Definitions and distinctions for health-related research","volume":"100","author":"Caspersen","year":"1985","journal-title":"Public Health Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3389\/fendo.2020.00491","article-title":"Sphingolipid metabolism and signaling in skeletal muscle: From physiology to physiopathology","volume":"11","author":"Guitton","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.cmet.2017.02.010","article-title":"Ceramide is metabolized to acylceramide and stored in lipid droplets","volume":"25","author":"Senkal","year":"2017","journal-title":"Cell Metab."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.3389\/fimmu.2020.576347","article-title":"Adipocyte ceramides\u2014The nexus of inflammation and metabolic disease","volume":"11","author":"Chaurasia","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3389\/fendo.2020.569250","article-title":"The role of ceramides in diabetes and cardiovascular disease regulation of ceramides by adipokines","volume":"11","author":"Field","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3389\/fendo.2020.00505","article-title":"Too much of a good thing? An evolutionary theory to explain the role of ceramides in nafld","volume":"11","author":"Poss","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/978-3-319-48382-5_12","article-title":"Insulin resistance, obesity and lipotoxicity","volume":"960","author":"Sezer","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.cmet.2020.10.001","article-title":"Central ceramide signaling mediates obesity-induced precocious puberty","volume":"32","author":"Heras","year":"2020","journal-title":"Cell Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E423","DOI":"10.1152\/ajpendo.00133.2016","article-title":"Targeting ceramide metabolism in obesity","volume":"311","author":"Aburasayn","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.2337\/db10-1221","article-title":"Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?","volume":"60","author":"Amati","year":"2011","journal-title":"Diabetes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cmet.2007.01.002","article-title":"Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance","volume":"5","author":"Holland","year":"2007","journal-title":"Cell Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"823071","DOI":"10.1155\/2014\/823071","article-title":"Endogenous ceramide contributes to the transcytosis of oxldl across endothelial cells and promotes its subendothelial retention in vascular wall","volume":"2014","author":"Li","year":"2014","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.cmet.2019.09.016","article-title":"Adipocyte hypoxia-inducible factor 2\u03b1 suppresses atherosclerosis by promoting adipose ceramide catabolism","volume":"30","author":"Zhang","year":"2019","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.tem.2015.07.006","article-title":"Ceramides\u2014Lipotoxic inducers of metabolic disorders","volume":"26","author":"Chaurasia","year":"2015","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_43","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_44","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.2337\/db17-1449","article-title":"Circulating sphingolipids, insulin, homa-ir, and homa-b: The strong heart family study","volume":"67","author":"Lemaitre","year":"2018","journal-title":"Diabetes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2337\/db08-1228","article-title":"Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance","volume":"58","author":"Haus","year":"2009","journal-title":"Diabetes"},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cmet.2007.02.005","article-title":"The path to insulin resistance: Paved with ceramides?","volume":"5","author":"Zierath","year":"2007","journal-title":"Cell Metab."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1126\/science.aav3722","article-title":"Targeting a ceramide double bond improves insulin resistance and hepatic steatosis","volume":"365","author":"Chaurasia","year":"2019","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.bcp.2018.04.026","article-title":"Racking up ceramide-induced islet \u03b2-cell dysfunction","volume":"154","author":"Kowluru","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_51","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_52","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_53","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s00125-015-3850-y","article-title":"Muscle sphingolipids during rest and exercise: A c18:0 signature for insulin resistance in humans","volume":"59","author":"Bergman","year":"2016","journal-title":"Diabetologia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e002395","DOI":"10.1136\/bmjdrc-2021-002395","article-title":"Ceramides and phospholipids are downregulated with liraglutide treatment: Results from the liraflame randomized controlled trial","volume":"9","author":"Zobel","year":"2021","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1016\/j.jacc.2021.03.314","article-title":"Fat-secreted ceramides regulate vascular redox state and influence outcomes in patients with cardiovascular disease","volume":"77","author":"Akawi","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1194\/jlr.P119000543","article-title":"Ldl subclass lipidomics in atherogenic dyslipidemia: Effect of statin therapy on bioactive lipids and dense ldl[s]","volume":"61","author":"Chapman","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E2335","DOI":"10.1210\/jc.2014-1665","article-title":"Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome","volume":"99","author":"Ng","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E45","DOI":"10.1210\/jc.2013-2559","article-title":"Molecular lipids identify cardiovascular risk and are efficiently lowered by simvastatin and pcsk9 deficiency","volume":"99","author":"Tarasov","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.amjcard.2020.04.052","article-title":"Effect of proprotein convertase subtilisin\/kexin type 9 inhibitors on plasma ceramide levels","volume":"128","author":"Ye","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"ref_61","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_62","doi-asserted-by":"crossref","unstructured":"Giera, M. (2018). Sphingolipid analysis in clinical research. Clinical Metabolomics: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-4939-7592-1"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5688","DOI":"10.1021\/ac5009964","article-title":"Improved sphingolipidomic approach based on ultra-high performance liquid chromatography and multiple mass spectrometries with application to cellular neurotoxicity","volume":"86","author":"Wang","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1194\/jlr.S087163","article-title":"Ms-based lipidomics of human blood plasma: A community-initiated position paper to develop accepted guidelines1","volume":"59","author":"Burla","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Carrard, J., Gallart-Ayala, H., Infanger, D., Teav, T., Wagner, J., Knaier, R., Colledge, F., Streese, L., K\u00f6nigstein, K., and Hinrichs, T. (2021). Metabolic view on human healthspan: A lipidome-wide association study. Metabolites, 11.","DOI":"10.3390\/metabo11050287"},{"key":"ref_66","unstructured":"(2021, September 01). Ceramides: A Class of Lipids with Links to Heart Disease. Available online: https:\/\/www.mayoclinic.org\/medical-professionals\/cardiovascular-diseases\/news\/ceramides-a-class-of-lipids-with-links-to-heart-disease\/mac-20429577."},{"key":"ref_67","unstructured":"Mi-Heart Ceramides (2021, September 01). Be in the Know. Now., Available online: https:\/\/news.mayocliniclabs.com\/ceramides-miheart\/#form-row-right."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e007931","DOI":"10.1161\/JAHA.117.007931","article-title":"Ceramide remodeling and risk of cardiovascular events and mortality","volume":"7","author":"Peterson","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1161\/CIRCULATIONAHA.116.023233","article-title":"Plasma lipidomic profiles improve on traditional risk factors for the prediction of cardiovascular events in type 2 diabetes mellitus","volume":"134","author":"Alshehry","year":"2016","journal-title":"Circulation"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1194\/jlr.P081281","article-title":"Plasma concentrations of molecular lipid species predict long-term clinical outcome in coronary artery disease patients","volume":"59","author":"Anroedh","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e005708","DOI":"10.1161\/CIRCHEARTFAILURE.118.005708","article-title":"Plasma ceramides and sphingomyelins in relation to heart failure risk","volume":"12","author":"Lemaitre","year":"2019","journal-title":"Circ. Heart Fail."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1194\/jlr.RA120000669","article-title":"Alterations in plasma triglycerides and ceramides: Links with cardiac function in humans with type 2 diabetes","volume":"61","author":"Peterson","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e013050","DOI":"10.1161\/JAHA.119.013050","article-title":"Association of circulating ceramides with cardiac structure and function in the community: The framingham heart study","volume":"8","author":"Nwabuo","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Hilvo, M., L\u00e4\u00e4peri, M., Jylh\u00e4, A., Kleber, M.E., Hurme, R., Scharnagl, H., M\u00e4rz, W., Sinisalo, J., and Laaksonen, R. (2021). Prior myocardial infarction, coronary artery disease extent, diabetes mellitus, and cert2 score for risk stratification in stable coronary artery disease. Eur. J. Prev. Cardiol., zwab122.","DOI":"10.1093\/eurjpc\/zwab122"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Gencer, B., Morrow, D.A., Braunwald, E., Goodrich, E.L., Hilvo, M., Kauhanen, D., Sabatine, M.S., Laaksonen, R., and O\u2019Donoghue, M.L. (2020). Plasma ceramide and phospholipid-based risk score and the risk of cardiovascular death in patients after acute coronary syndrome. Eur J. Prev. Cardiol., zwaa143.","DOI":"10.1093\/eurjpc\/zwaa143"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Leiherer, A., M\u00fcndlein, A., Laaksonen, R., L\u00e4\u00e4peri, M., Jylh\u00e4, A., Fraunberger, P., and Drexel, H. (2021). Comparison of recent ceramide-based coronary risk prediction scores in cardiovascular disease patients. Eur. J. Prev. Cardiol., zwab112.","DOI":"10.1093\/eurjpc\/zwab112"},{"key":"ref_77","unstructured":"SCORE2 Working Group, and ESC Cardiovascular Risk Collaboration (2021). Score2 risk prediction algorithms: New models to estimate 10-year risk of cardiovascular disease in Europe. Eur. Heart J., 42, 2439\u20132454."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.3389\/fphys.2020.01104","article-title":"Circulating ceramide: A new cardiometabolic biomarker in patients with comorbid acute coronary syndrome and type 2 diabetes mellitus","volume":"11","author":"Cao","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jacl.2020.01.005","article-title":"Ceramides and risk of major adverse cardiovascular events: A meta-analysis of longitudinal studies","volume":"14","author":"Mantovani","year":"2020","journal-title":"J. Clin. Lipidol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/eurheartj\/ehz525","article-title":"Risky lipids: Refining the ceramide score that measures cardiovascular health","volume":"41","author":"Poss","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S147","DOI":"10.1016\/j.molmet.2019.06.008","article-title":"Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion\u2014A step towards precision medicine","volume":"27","author":"Thorens","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1016\/j.celrep.2017.02.019","article-title":"Plasma dihydroceramides are diabetes susceptibility biomarker candidates in mice and humans","volume":"18","author":"Wigger","year":"2017","journal-title":"Cell Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"628","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_85","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/S0140-6736(16)30383-X","article-title":"Lancet Physical Activity Series 2 Executive Committee. The economic burden of physical inactivity: A global analysis of major non-communicable diseases","volume":"388","author":"Ding","year":"2016","journal-title":"Lancet"},{"key":"ref_86","unstructured":"Merkur, S., Sassi, F., and McDaid, D. (2013). Promoting Health, Preventing Disease: Is there an Economic Case?, WHO."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1024\/1661-8157\/a003061","article-title":"Physical activity is an opportunity for the health of nations: What should we do next?","volume":"107","author":"Gojanovic","year":"2018","journal-title":"Praxis"},{"key":"ref_88","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_89","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1113\/expphysiol.2003.002605","article-title":"Exercise and training effects on ceramide metabolism in human skeletal muscle","volume":"89","author":"Helge","year":"2004","journal-title":"Exp. Physiol."},{"key":"ref_90","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_91","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_92","doi-asserted-by":"crossref","first-page":"E99","DOI":"10.1152\/ajpendo.00587.2005","article-title":"Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content","volume":"291","author":"Bruce","year":"2006","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"E882","DOI":"10.1152\/ajpendo.00769.2007","article-title":"Exercise-induced alterations in intramyocellular lipids and insulin resistance: The athlete\u2019s paradox revisited","volume":"294","author":"Amati","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1002\/cam4.773","article-title":"Measured cardiorespiratory fitness and self-reported physical activity: Associations with cancer risk and death in a long-term prospective cohort study","volume":"5","author":"Robsahm","year":"2016","journal-title":"Cancer Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/j.mayocp.2015.07.017","article-title":"Association of cardiorespiratory fitness with coronary heart disease in asymptomatic men","volume":"90","author":"Gander","year":"2015","journal-title":"Mayo Clin. Proc."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1161\/CIRCHEARTFAILURE.112.000088","article-title":"Cardiorespiratory fitness, body mass index, and heart failure mortality in men","volume":"6","author":"Farrell","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e653","DOI":"10.1161\/CIR.0000000000000461","article-title":"Importance of assessing cardiorespiratory fitness in clinical practice: A case for fitness as a clinical vital sign: A scientific statement from the american heart association","volume":"134","author":"Ross","year":"2016","journal-title":"Circulation"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e001268","DOI":"10.1161\/JAHA.114.001268","article-title":"Physical fitness and hypertension in a population at risk for cardiovascular disease: The henry ford exercise testing (fit) project","volume":"3","author":"Juraschek","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.jpeds.2006.12.039","article-title":"Relationship of physical activity, fitness, and fatness with clustered metabolic risk in children and adolescents: The european youth heart study","volume":"150","author":"Rizzo","year":"2007","journal-title":"J. Pediatr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.amjmed.2004.06.047","article-title":"Fitness versus physical activity patterns in predicting mortality in men","volume":"117","author":"Myers","year":"2004","journal-title":"Am. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1136\/bjsm.2009.066209","article-title":"Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women","volume":"45","author":"Lee","year":"2011","journal-title":"Br. J. Sports Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1097\/00005768-200105000-00012","article-title":"Physical fitness and activity as separate heart disease risk factors: A meta-analysis","volume":"33","author":"Williams","year":"2001","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1112.e1116","DOI":"10.1016\/j.cell.2020.04.043","article-title":"Molecular choreography of acute exercise","volume":"181","author":"Contrepois","year":"2020","journal-title":"Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1161\/CIRCULATIONAHA.120.050281","article-title":"Metabolic architecture of acute exercise response in middle-aged adults in the community","volume":"142","author":"Nayor","year":"2020","journal-title":"Circulation"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/gerona\/gly273","article-title":"Association between sphingolipids and cardiopulmonary fitness in coronary artery disease patients undertaking cardiac rehabilitation","volume":"75","author":"Saleem","year":"2018","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/acel.12491","article-title":"Circulating ceramides are inversely associated with cardiorespiratory fitness in participants aged 54-96 years from the baltimore longitudinal study of aging","volume":"15","author":"Fabbri","year":"2016","journal-title":"Aging Cell"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Contaifer, D., Buckley, L.F., Wohlford, G., Kumar, N.G., Morriss, J.M., Ranasinghe, A.D., Carbone, S., Canada, J.M., Trankle, C., and Abbate, A. (2019). Metabolic modulation predicts heart failure tests performance. PLoS ONE, 14.","DOI":"10.1101\/555417"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/10\/675\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:08:13Z","timestamp":1760166493000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/10\/675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,30]]},"references-count":107,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["metabo11100675"],"URL":"https:\/\/doi.org\/10.3390\/metabo11100675","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,30]]}}}