title: Endogenous synthesis of n-3 polyunsaturated fatty acids in Fat-1 mice is associated with increased mammary gland and liver syndecan-1.
abstract: Long chain n-3 PUFA have been shown to have chemopreventive properties against breast cancer through various mechanisms. One pathway, studied in human breast cancer cell lines, involves upregulation of the proteoglycan, syndecan-1 (SDC-1) by n-3 PUFA-enriched LDL. Using Fat-1 mice that are able to convert n-6 to n-3 PUFA, we tested whether SDC-1 level in vivo is elevated in mammary glands due to endogenously synthesized rather than LDL-derived n-3 PUFA. Female Fat-1 and wild type (wt) mice were fed an n-6 PUFA- enriched diet for 7 weeks. Fatty acid analysis of plasma lipoproteins showed that total n-6 PUFA reflected dietary intake similarly in both genotypes (VLDL, 36.2±2.2 and 40.9±3.9; LDL, 49.0±3.3 and 48.1±2.0; HDL, 54.6±1.2 and 58.2±1.3, mean ± SEM percent of total fatty acids for Fat-1 and wt animals respectively). Lipoprotein percent n-3 PUFA was also similar between groups. However, phospholipids and triglycerides extracted from mammary and liver tissues demonstrated significantly higher n-3 PUFA and a corresponding decrease in the ratio n-6/n-3 PUFA in Fat-1 compared to wt mice. This was accompanied by higher SDC-1 in mammary glands and livers of Fat-1 mice, thus demonstrating that endogenously synthesized n-3 PUFA may upregulate SDC-1 in the presence of high dietary n-6 PUFA.
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Haiguo
authors.initials: H
authors.lastname: Sun
authors.forename: Yunping
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Gu
authors.forename: Martha D
authors.initials: MD
authors.lastname: Wilson
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Chen
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Rudel
authors.forename: Mark C
authors.initials: MC
authors.lastname: Willingham
authors.forename: Iris J
authors.initials: IJ
authors.lastname: Edwards
mesh_terms: D000818:Animals; D015153:Blotting, Western; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000235:genetics*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010743:Phospholipids / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D015525:Fatty Acids, Omega-3; D010743:Phospholipids; D053668:Syndecan-1; D014280:Triglycerides; C466741:fat-1 protein, C elegans; D002784:Cholesterol; D044943:Fatty Acid Desaturases