File S1 - Lipid Profiling following Intake of the Omega 3 Fatty Acid DHA Identifies the Peroxidized Metabolites F4-Neuroprostanes as the Best Predictors of Atherosclerosis Prevention

Figure S1, Correlations between doses of DHA given to LDLR-/- mice and plasma levels of PUFA and of AA, EPA, and DHA and their corresponding oxylipins. Figure S2, Correlations between plasma levels of EPA, and their corresponding specific oxylipins. Figure S3, Correlations between plasma levels of DHA, and their corresponding specific oxylipins. Figure S4, Correlations between doses of DHA given to LDLR-/- mice and liver levels of PUFA and plasma levels of n-6 PUFA, n-3 PUFA and DHA and their corresponding peroxidized metabolites. Figure S5, Partial least squares discrimination analysis of dietary groups in LDLR-/- given by daily oral gavages increasing doses of DHA. (A) Animals eating each dietary mixture with complete data sets (n = 10/group) were segregated by PLS analyses. (B) Group segregation was driven by plasma (yellow triangle) and liver (orange triangle) metabolites belonging to clusters C2, C3, and C4 as identified in Figure 7. The plasma EPA metabolite, 17,18-dihydroxyeicosaotetraenoic acid (17,18-DiHETE) and the liver DHA metabolite group F4-neuroprostanes (F4-NeuroPs) were the most frequently selected variables occurring in 80% and 60% of models, respectively. Figure S6, Correlation between plasma F2-isoprostanes and 9-HETE levels. Figure S7, Correlations between plasma oxylipins and plasma 9-HETE levels. Table S1, Surrogates recoveries. Table S2, Oxylipin assay UPLC solvent gradient. Table S3, UPLC/MS-MS parameters of metabolites measured in plasma. Table S4, Concentrations of plasma* and liver† triglycerides (TG) and total cholesterol (TC). Table S5, Changes in systolic and diastolic blood pressures (sBP and dBP), and heart rate (HR). Table S6, Plasma and liver levels of major polyunsaturated fatty acids (PUFA). LDLR-/- mice were given by daily oral gavages (20 weeks) either oleic acid rich sunflower oil (Control group) or a mixture of oleic acid rich sunflower oil and DHA rich tuna oil providing 0.1%, 1% or 2% of energy as DHA (DHA1, DHA2, and DHA3 groups respectively). Table S7, Plasma levels of PUFAs-derived oxylipins. LDLR-/- mice were given by daily oral gavages (20 weeks) either oleic acid rich sunflower oil (Control group) or a mixture of oleic acid rich sunflower oil and DHA rich tuna oil providing 0.1%, 1% or 2% of energy as DHA (DHA1, DHA2, and DHA3 groups respectively). Table S8, Thromboxane and prostaglandin stability through sample processing. Table S9, Fatty acid triol stability through sample processing. Table S10, Fatty acid diol stability through sample processing. (DOCX)