biostudies-literatureChattopadhyay ANHLBINational Institute of Diabetes and Digestive and Kidney DiseasesU.S. Public Health ServiceNational Institutes of HealthUniversity of California, Los AngelesU.S. Department of Veterans AffairsCSRD VA100370https://www.ebi.ac.uk/biostudies/studies/S-EPMC10200992biostudies-literatureUnknown64(5)Conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA) by autotaxin, a secreted phospholipase D, is a major pathway for producing LPA. We previously reported that feeding Ldlr^-/- mice standard mouse chow supplemented with unsaturated LPA or lysophosphatidylcholine qualitatively mimicked the dyslipidemia and atherosclerosis induced by feeding a Western diet (WD). Here, we report that adding unsaturated LPA to standard mouse chow also increased the content of reactive oxygen species and oxidized phospholipids (OxPLs) in jejunum mucus. To determine the role of intestinal autotaxin, enterocyte-specific Ldlr^-/-/Enpp2 KO (intestinal KO) mice were generated. In control mice, the WD increased enterocyte Enpp2 expression and raised autotaxin levels. Ex vivo, addiJournal of lipid researchRole of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis.PMC10200992CDA2 IK2CX001717IK2 CX0017171R01 HL148286P30 DK041301Sulaiman DMoolenaar WHJacobs JPDelk SReddy STNavab MMukherjee PWang HDorreh NFogelman AMChattopadhyay AGirjalva VfalseRole of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis.Conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA) by autotaxin, a secreted phospholipase D, is a major pathway for producing LPA. We previously reported that feeding Ldlr^-/- mice standard mouse chow supplemented with unsaturated LPA or lysophosphatidylcholine qualitatively mimicked the dyslipidemia and atherosclerosis induced by feeding a Western diet (WD). Here, we report that adding unsaturated LPA to standard mouse chow also increased the content of reactive oxygen species and oxidized phospholipids (OxPLs) in jejunum mucus. To determine the role of intestinal autotaxin, enterocyte-specific Ldlr^-/-/Enpp2 KO (intestinal KO) mice were generated. In control mice, the WD increased enterocyte Enpp2 expression and raised autotaxin levels. Ex vivo, addi2023-01-01T00:00:00Z2023 May2025-04-04T10:27:32.042Z2025-04-04T10:27:32.042ZS-EPMC102009923705933310.1016/j.jlr.2023.100370