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Endogenous synthesis of n-3 polyunsaturated fatty acids in Fat-1 mice is associated with increased mammary gland and liver syndecan-1.

Sun H, Hu Y, Gu Z, Wilson MD, Chen YQ, Rudel LL, Willingham MC, Edwards IJ - PLoS ONE (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.

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.

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Fatty acid composition of whole plasma (WP) and lipoproteins of Fat-1 and wild type (wt) mice fed a chow control (A, B) and n-6 PUFA-enriched diet (C, D).Lipoproteins were isolated by gel filtration chromatography and fatty acids were measured as methyl esters by gas chromatography. Bars represent the means ± SEM of A and C, total n-3 PUFA (eicosapentaenoic acid, 20∶5; docosapentaenoic acid, 22∶5; docosahexaenoic acid, 22∶6); B and D, ratio of n-6 PUFA (linoleic acid, 18∶2+ arachidonic acid, 20∶4) to n-3 PUFA . * P<0.05 Fat-1 versus wt by Student's t test.
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pone-0020502-g001: Fatty acid composition of whole plasma (WP) and lipoproteins of Fat-1 and wild type (wt) mice fed a chow control (A, B) and n-6 PUFA-enriched diet (C, D).Lipoproteins were isolated by gel filtration chromatography and fatty acids were measured as methyl esters by gas chromatography. Bars represent the means ± SEM of A and C, total n-3 PUFA (eicosapentaenoic acid, 20∶5; docosapentaenoic acid, 22∶5; docosahexaenoic acid, 22∶6); B and D, ratio of n-6 PUFA (linoleic acid, 18∶2+ arachidonic acid, 20∶4) to n-3 PUFA . * P<0.05 Fat-1 versus wt by Student's t test.

Mentions: The effects of the n-6 PUFA enriched diet on plasma lipoproteins are shown in Fig. 1. When Fat-1 and wt mice were fed a commercial chow control diet (n-6 to n-3 ratio, approximately 5-8 to 1) significantly higher n-3 PUFA were measured in the whole plasma of Fat-1 compared to wt mice (Fig. 1A). This was presumably due in part to elevated n-3 PUFA free fatty acids because percent n-3 PUFA in isolated lipoproteins was similar between Fat-1 and wt mice. In agreement with these data, n-6/n-3 ratios in Fat-1 compared to wt mice were significantly lower in whole plasma only and not in isolated lipoproteins (Fig. 1B). Seven weeks of the n-6 PUFA diet (n-6 to n-3 ratio of 40) resulted in an elevation in plasma n-6 PUFA with a corresponding decrease in n-3 PUFA for both genotypes (Fig. 1C versus 1A). A similar reduction in percent n-3 PUFA for Fat-1 and wt mice was observed for all lipoprotein species. This resulted in a marked increase in the n-6/n-3 PUFA ratios of whole plasma and isolated lipoproteins with no differences in response between the genotypes (Fig. 1D versus 1B). Thus the lipoproteins directly reflected dietary PUFA intake with little influence of the fat-1 transgene.


Endogenous synthesis of n-3 polyunsaturated fatty acids in Fat-1 mice is associated with increased mammary gland and liver syndecan-1.

Sun H, Hu Y, Gu Z, Wilson MD, Chen YQ, Rudel LL, Willingham MC, Edwards IJ - PLoS ONE (2011)

Fatty acid composition of whole plasma (WP) and lipoproteins of Fat-1 and wild type (wt) mice fed a chow control (A, B) and n-6 PUFA-enriched diet (C, D).Lipoproteins were isolated by gel filtration chromatography and fatty acids were measured as methyl esters by gas chromatography. Bars represent the means ± SEM of A and C, total n-3 PUFA (eicosapentaenoic acid, 20∶5; docosapentaenoic acid, 22∶5; docosahexaenoic acid, 22∶6); B and D, ratio of n-6 PUFA (linoleic acid, 18∶2+ arachidonic acid, 20∶4) to n-3 PUFA . * P<0.05 Fat-1 versus wt by Student's t test.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3105073&req=5

pone-0020502-g001: Fatty acid composition of whole plasma (WP) and lipoproteins of Fat-1 and wild type (wt) mice fed a chow control (A, B) and n-6 PUFA-enriched diet (C, D).Lipoproteins were isolated by gel filtration chromatography and fatty acids were measured as methyl esters by gas chromatography. Bars represent the means ± SEM of A and C, total n-3 PUFA (eicosapentaenoic acid, 20∶5; docosapentaenoic acid, 22∶5; docosahexaenoic acid, 22∶6); B and D, ratio of n-6 PUFA (linoleic acid, 18∶2+ arachidonic acid, 20∶4) to n-3 PUFA . * P<0.05 Fat-1 versus wt by Student's t test.
Mentions: The effects of the n-6 PUFA enriched diet on plasma lipoproteins are shown in Fig. 1. When Fat-1 and wt mice were fed a commercial chow control diet (n-6 to n-3 ratio, approximately 5-8 to 1) significantly higher n-3 PUFA were measured in the whole plasma of Fat-1 compared to wt mice (Fig. 1A). This was presumably due in part to elevated n-3 PUFA free fatty acids because percent n-3 PUFA in isolated lipoproteins was similar between Fat-1 and wt mice. In agreement with these data, n-6/n-3 ratios in Fat-1 compared to wt mice were significantly lower in whole plasma only and not in isolated lipoproteins (Fig. 1B). Seven weeks of the n-6 PUFA diet (n-6 to n-3 ratio of 40) resulted in an elevation in plasma n-6 PUFA with a corresponding decrease in n-3 PUFA for both genotypes (Fig. 1C versus 1A). A similar reduction in percent n-3 PUFA for Fat-1 and wt mice was observed for all lipoprotein species. This resulted in a marked increase in the n-6/n-3 PUFA ratios of whole plasma and isolated lipoproteins with no differences in response between the genotypes (Fig. 1D versus 1B). Thus the lipoproteins directly reflected dietary PUFA intake with little influence of the fat-1 transgene.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.

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.

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Related in: MedlinePlus