{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:10:01Z","timestamp":1790763001414,"version":"4.1.0"},"reference-count":150,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"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>Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the main causes of chronic liver disease worldwide. NAFLD comprises a group of conditions characterized by the accumulation of hepatic lipids that can eventually lead to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), the fifth most common cancer type with a poor survival rate. In this context, several works have pointed out perturbations in lipid metabolism and, particularly, changes in bioactive sphingolipids, as a hallmark of NAFLD and derived HCC. In the present work, we have reviewed existing literature about sphingolipids and the development of NAFLD and NAFLD-derived HCC. During metabolic syndrome, considered a risk factor for steatosis development, an increase in ceramide and sphigosine-1-phosphate (S1P) have been reported. Likewise, other reports have highlighted that increased sphingomyelin and ceramide content is observed during steatosis and NASH. Ceramide also plays a role in liver fibrosis and cirrhosis, acting synergistically with S1P. Finally, during HCC, metabolic fluxes are redirected to reduce cellular ceramide levels whilst increasing S1P to support tumor growth.<\/jats:p>","DOI":"10.3390\/ijms21010040","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T09:50:33Z","timestamp":1576835433000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["Sphingolipids in Non-Alcoholic Fatty Liver Disease and Hepatocellular Carcinoma: Ceramide Turnover"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0404-6244","authenticated-orcid":false,"given":"Jorge","family":"Simon","sequence":"first","affiliation":[{"name":"Liver Disease and Liver Metabolism Lab, CIC bioGUNE, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4359-1704","authenticated-orcid":false,"given":"Alberto","family":"Ouro","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV\/EHU), 48980 Leioa, Bizkaia, Spain"},{"name":"Instituto Biofisika (UPV\/EHU, CSIC), University of the Basque Country, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lolia","family":"Ala-Ibanibo","sequence":"additional","affiliation":[{"name":"Liver Disease and Liver Metabolism Lab, CIC bioGUNE, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Presa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV\/EHU), 48980 Leioa, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9204-581X","authenticated-orcid":false,"given":"Teresa Cardoso","family":"Delgado","sequence":"additional","affiliation":[{"name":"Liver Disease and Liver Metabolism Lab, CIC bioGUNE, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Luz","family":"Mart\u00ednez-Chantar","sequence":"additional","affiliation":[{"name":"Liver Disease and Liver Metabolism Lab, CIC bioGUNE, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease\u2014Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000282080","article-title":"Epidemiology of non-alcoholic fatty liver disease","volume":"28","author":"Bellentani","year":"2010","journal-title":"Dig. 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