A lipidomic cell-based assay for studying drug-induced phospholipidosis and steatosis

Electrophoresis
Juan Carlos García-CañaverasAgustín Lahoz

Abstract

Phospholipidosis and steatosis are two toxic effects, which course with overaccumulation of different classes of lipids in the liver. MS-based lipidomics has become a powerful tool for the comprehensive determination of lipids. LC-MS lipid profiling of HepG2 cells is proposed as an in vitro 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-known 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 ...Continue Reading

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Citations

Aug 8, 2018·Neurochemical Research·Blaise W Menta, Russell H Swerdlow
Jan 28, 2018·Clinical and Translational Medicine·Todd A Lydic, Young-Hwa Goo
May 19, 2020·Critical Reviews in Toxicology·Xihui ZhangLeshuai W Zhang
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Mar 19, 2020·Frontiers in Cell and Developmental Biology·Marie ClémotD Leanne Jones
Feb 6, 2021·International Journal of Molecular Sciences·Sara CasatiAnna T Brini

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