Lipidomic analysis of human primary hepatocytes following LXR activation with GW3965 identifies AGXT2L1 as a main target associated to changes in phosphatidylethanolamine

Publication date: Available online 26 November 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Deolinda Santinha, Anna Klopot, Igor Marques, Ewa Ellis, Carl Jorns, Helene Johansson, Tânia Melo, Per Antonson, Tomas Jakobsson, Vítor Félix, Jan-Åke Gustafsson, Maria Rosário Domingues, Agneta Mode, Luisa A. HelgueroAbstractLiver X receptor (LXR) agonists have the potential to alleviate obesity related diseases, particularly atherosclerosis. However, LXRs are transcriptional regulators that induce de novo lipogenesis and lipid accumulation in hepatocytes which represents a serious adverse effect. In this work, we sought to characterize the LXR agonist GW3965 effects on fatty acid (FA) and phospholipid (PL) remodelling and the correlation with gene expression in order to better understand the underlying effects leading to hepatic pathology upon LXR activation. Human primary hepatocytes treated for 48 h with GW3965 were analysed for changes in lipid metabolism gene expression by qPCR, variations in the FA profile was evaluated by GC-FID and in PL profiles using thin layer chromatography, ESI-MS and MS/MS analysis. Changes in cell membrane biochemical properties were studied using bilayer models generated with CHARMM-GUI. ELOLV6 and SCD1 mRNA increase was consistent with higher C16:1 and C18:1n9 at the expense of C16:0 and C18:0. The reduction of C18:2n6 and increase in C20:2n6 was in agreement with ELOVL5 upregulation. Phosphatydilethanolamine ...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research