4092a633b1310b3de3bb0052d4311c40 289310.pdf 22c1b92a5170e05191581f28e141bd21d9f82dd6 289310.pdf a5be40af3eece60319c4dbd6210c7f569bee62367e3cb1dfb3766854ea6ac5ae 289310.pdf Title: Phytosterols and Omega 3 Supplementation Exert Novel Regulatory Effects on Metabolic and Inflammatory Pathways: A Proteomic Study Subject: Cardiovascular disease (CVD) remains one of the major causes of death and disability worldwide. In addition to drug treatment, nutritional interventions or supplementations are becoming a health strategy for CVD prevention. Phytosterols (PhyS) are natural components that have been shown to reduce cholesterol levels; while poly-unsaturated fatty acids (PUFA), mainly omega-3 (3) fatty acids, have shown to reduce triglyceride levels. Here we aimed to investigate whether the proteins in the main lipoproteins (low density lipoproteins (LDL) and high density lipoproteins (HDL)) as well as proteins in the lipid free plasma fraction (LPDP) were regulated by the intake of PhyS-milk or 3-milk, in overweight healthy volunteers by a proteomic based systems biology approach. The study was a longitudinal crossover trial, including thirty-two healthy volunteers with body mass index (BMI) 25–35 kg/m2 (Clinical Trial: ISRCTN78753338). Basal samples before any intervention and after 4 weeks of intake of PhyS or 3-milk were analyzed. Proteomic profiling by two dimensional electrophoresis (2-DE) followed by mass spectrometry-(MALDI/TOF), ELISA, Western blot, conventional biochemical analysis, and in-silico bioinformatics were performed. The intake of PhyS-milk did not induce changes in the lipid associated plasma protein fraction, whereas 3-milk significantly increased apolipoprotein (Apo)- E LDL content (p = 0.043) and induced a coordinated increase in several HDL-associated proteins, Apo A–I, lecitin cholesterol acyltransferase (LCAT), paraoxonase-1 (PON-1), Apo D, and Apo L1 (p < 0.05 for all). Interestingly, PhyS-milk intake induced a reduction in inflammatory molecules not seen after 3-milk intake. Serum amyloid P component (SAP) was reduced in the LPDP protein fraction (p = 0.001) of subjects taking PhyS-milk and C-C motif chemokine 2 (CCL2)expression detected by reverse transcription polymerase chain reaction (RT-PCR) analysis in white blood cells was significantly reduced (p = 0.013). No changes were observed in the lipid-free plasma proteome with 3-milk. Our study provides novel results and highlights that the PhyS-milk induces attenuation of the pro-inflammatory pathways, whereas 3-milk induces improvement in lipid metabolic pathways. Keywords: phytosterols; omega 3; HDL; LDL; inflammation; lipid metabolism Author: Carmen Lambert, Judit Cubedo, Teresa Padró, Joan Sánchez-Hernández, Rosa M. Antonijoan, Antonio Perez and Lina Badimon Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.15 CreationDate: Wed Jun 14 05:09:13 2017 CEST ModDate: Wed Jun 14 05:09:13 2017 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2978192 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JCIHIT+URWPalladioL-Ital Type 1 Custom yes yes no 97 0 GRDVGT+URWPalladioL-Bold Type 1 Custom yes yes no 98 0 ENXZUH+VnURWPalladioL-Bold Type 1 Custom yes yes no 99 0 ABKTOJ+URWPalladioL-Roma Type 1 Custom yes yes no 100 0 PMTDSU+EURM10 Type 1 Builtin yes yes no 101 0 HGMNRX+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 105 0 NYWBCD+EURB10 Type 1 Builtin yes yes no 185 0 XEYJZU+CMSY10 Type 1 Builtin yes yes no 186 0 AZBFJT+VnURWPalladioL Type 1 Custom yes yes no 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