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Long term phytosterol treatment alters global gene expression in the liver of apo E deficient mice
Author(s) -
Xu Zuyuan,
Moghadasian Mohammed
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1105
Subject(s) - phytosterol , endocrinology , medicine , gene expression , cholesterol , microarray , pathogenesis , lipid metabolism , metabolism , biology , apolipoprotein e , gene , apolipoprotein b , biochemistry , disease
Background: We have consistently observed that dietary phytosterols significantly reduce plasma cholesterol concentrations and atherosclerosis in apo E‐KO mice. We investigated long‐term effects of phytosterol treatment on gene expression in the liver of these mice. Methods: Male apo E‐KO mice were fed an atherogenic diet supplemented with (n=8) or without (n=7) 2% (w/w) phytosterol mixtures for 14 weeks. Liver specimens were collected and frozen immediately. mRNA was extracted from these samples, and subjected to microarray analyses. Results: The expression of 137 genes was significantly changed in the phytosterol‐treated group, as compared to controls. Various database searches indicated that these genes are involved in a number of metabolic pathways including lipid metabolism, inflammation, glucose metabolism, protein metabolism, heme biosynthesis and others. These changes were associated with significant reductions in plasma cholesterol levels and the severity of atherosclerosis. Conclusions: Anti‐atherogenic and cholesterol‐lowering effects of plant sterols in apo E‐KO mice may be mediated through beneficial alterations in the expression of genes in various pathways involved in pathogenesis of atherosclerosis. Further studies warrant mechanisms by which dietary phytosterols regulate gene expression. Acknowledgements: Supported by NSERC, CIHR, and Heart and Stroke Foundation.