{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:32:31Z","timestamp":1787315551959,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2017,6,8]],"date-time":"2017-06-08T00:00:00Z","timestamp":1496880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/0026"],"award-info":[{"award-number":["PI14\/0026"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI13\/0986"],"award-info":[{"award-number":["PI13\/0986"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001258","name":"Roche Organ Transplant Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001258","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Electrophoresis"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Phospholipidosis and steatosis are two toxic effects, which course with overaccumulation of different classes of lipids in the liver. MS\u2010based lipidomics has become a powerful tool for the comprehensive determination of lipids. LC\u2010MS lipid profiling of HepG2 cells is proposed as an\n                    <jats:italic>in vitro<\/jats:italic>\n                    assay to study and anticipate phospholipidosis and steatosis. Cells with and without preincubation with a mixture of free fatty acids (FFA; i.e. oleic and palmitic) were exposed to a set of well\u2010known steatogenic and phospholipidogenic compounds. The use of FFA preloading accelerated the accumulation of phospholipids, thus leading to a better discrimination of phospholipidosis, and magnified the lipidomic alterations induced by steatogenic drugs. Phospholipidosis was characterized by increased levels of phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, and phosphatidylinositols, while steatosis induced alterations in FA oxidation and triacylglyceride (TG) synthesis pathways (with changes in the levels of FFA, acylcarnitines, monoacylglycerides, diacylglycerides, and TG). Interestingly, palmitic and oleic acids incorporation into lipids differed. A characteristic pattern was observed in the fold of change of particular TG species in the case of steatosis (TG(54:3)\u00a0&gt;\u00a0TG(52:2)\u00a0&gt;\u00a0TG(50:1)\u00a0&gt;\u00a0TG(48:0)). Based on the levels of those lipids containing only palmitic and\/or oleic acid moieties a partial least squares\u2010discriminant analysis model was built, which showed good discrimination among nontoxic, phospholipidogenic and steatogenic compounds. In conclusion, it has been shown that the use of FFA preincubation together with intracellular LC\u2010MS based lipid profiling could be a useful approach to identify the potential of drug candidates to induce phospholipidosis and\/or steatosis.\n                  <\/jats:p>","DOI":"10.1002\/elps.201700079","type":"journal-article","created":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T04:23:13Z","timestamp":1494994993000},"page":"2331-2340","source":"Crossref","is-referenced-by-count":24,"title":["A lipidomic cell\u2010based assay for studying drug\u2010induced phospholipidosis and steatosis"],"prefix":"10.1002","volume":"38","author":[{"given":"Juan Carlos","family":"Garc\u00eda\u2010Ca\u00f1averas","sequence":"first","affiliation":[{"name":"Unidad de Biomarcadores y Medicina de Precisi\u00f3n, Unidad Anal\u00edtica, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Hospital La Fe  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel David","family":"Peris\u2010D\u00edaz","sequence":"additional","affiliation":[{"name":"Unidad de Biomarcadores y Medicina de Precisi\u00f3n, Unidad Anal\u00edtica, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Hospital La Fe  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Isabel","family":"Alcoriza\u2010Balaguer","sequence":"additional","affiliation":[{"name":"Unidad de Biomarcadores y Medicina de Precisi\u00f3n, Unidad Anal\u00edtica, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Hospital La Fe  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Cerd\u00e1n\u2010Calero","sequence":"additional","affiliation":[{"name":"Unidad de Biomarcadores y Medicina de Precisi\u00f3n, Unidad Anal\u00edtica, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Hospital La Fe  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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