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Menhaden oil, but not safflower or soybean oil, aids in restoring the polyunsaturated fatty acid profile in the novel delta-6-desaturase mouse.

Monteiro J, Li FJ, Maclennan M, Rabalski A, Moghadasian MH, Nakamura MT, Ma DW - Lipids Health Dis (2012)

Bottom Line: Growing evidence suggests that individual PUFA may have independent effects in health and disease.Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice.Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.

ABSTRACT

Background: Polyunsaturated fatty acids (PUFA) have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA, linoleic acid (LA) and α-linolenic acid (ALA), have been difficult to discern from the actions of their highly unsaturated fatty acid (HUFA) downstream metabolites. This issue has recently been addressed through the development of the Δ-6 desaturase knock out (D6KO) mouse, which lacks the rate limiting Δ-6 desaturase enzyme and therefore cannot metabolize LA or ALA. However, a potential confounder in this model is the production of novel Δ-5 desaturase (D5D) derived fatty acids when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid.

Objective: The aim of the present study was to characterize how the D6KO model differentially responds to diets containing the essential n-6 and n-3 PUFA, and whether the direct provision of downstream HUFA can rescue the phenotype and prevent the production of D5D fatty acids.

Methodology: Liver and serum phospholipid (PL) fatty acid composition was examined in D6KO and wild type mice fed i) 10% safflower oil diet (SF, LA rich) ii) 10% soy diet (SO, LA+ALA) or iii) 3% menhaden oil +7% SF diet (MD, HUFA rich) for 28 days (n = 3-7/group).

Results: Novel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice.

Conclusions: Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

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Preferential distribution of 3 novel D5D fatty acids among the liver phospholipid fractions of D6KO mice across dietary treatment groups. A) Distribution of 20:3 (Δ7,11,14); B) distribution of 20:4 (Δ7,11,14,17); C) distribution of 22:4 (Δ9,13,16,19).
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Figure 3: Preferential distribution of 3 novel D5D fatty acids among the liver phospholipid fractions of D6KO mice across dietary treatment groups. A) Distribution of 20:3 (Δ7,11,14); B) distribution of 20:4 (Δ7,11,14,17); C) distribution of 22:4 (Δ9,13,16,19).

Mentions: Based on previously published results [17], three peaks corresponding to three Δ-5 desaturase (D5D) derived fatty acids [20:3n6 (Δ7, 11, 14), 20:4n3 (Δ7, 11, 14, 17) and 22:4n3 (Δ9, 13, 16, 19)] were found in the liver PL fractions of D6KO mice fed LA-rich safflower oil (SF) and LA+ALA-enriched soybean oil (SO) diets (Figure 2; Figure 3). These three fatty acids were absent from all three experimental diets, and were also absent in the chromatographs of WT SF and SO fed mice. All three novel fatty acids were found to be differentially distributed among the six PL fractions (PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine; PI, phosphatidylinositol; SM, sphingomyelin; Lyso-PC, lyso-phosphatidylcholine). The PI fraction contained the highest percentage of 20:3n6 (Δ7, 11, 14) (SO =23.5 + 4.4%; SF = 30.6 + 1.6%) followed by the PS (17.7 + 1.6%), PE (11.7 + 1.7%), SM (8.4 + 3.2%), Lyso-PC (4.8 + 1.0%), and PC factions (4.1 + 0.6%) in SO-fed D6KO mice; and followed by PS (20.9 + 2.2%), PE (13.4 + 0.7%), PC (5.4 + 0.4%), SM (5.0 + 3.7%), and Lyso-PC fractions (4.0 + 1.7%) in SF-fed D6KO mice (Figure 3A). In the PI fraction of D6KO mice fed SF, 20:3n6 (Δ7, 11, 14) comprised almost a third of all fatty acids, and in the PI fraction of SO-fed D6KO mice, this novel fatty acid accounted for almost a fourth of total fatty acids. 20:4n3 (Δ7, 11, 14, 17) and 22:4n3 (Δ9, 13, 16, 19) were also selectively distributed across PL fractions, with the highest levels (relative to total fatty acids) found in PE, PI and PS fractions (Figure 3B,C).


Menhaden oil, but not safflower or soybean oil, aids in restoring the polyunsaturated fatty acid profile in the novel delta-6-desaturase mouse.

Monteiro J, Li FJ, Maclennan M, Rabalski A, Moghadasian MH, Nakamura MT, Ma DW - Lipids Health Dis (2012)

Preferential distribution of 3 novel D5D fatty acids among the liver phospholipid fractions of D6KO mice across dietary treatment groups. A) Distribution of 20:3 (Δ7,11,14); B) distribution of 20:4 (Δ7,11,14,17); C) distribution of 22:4 (Δ9,13,16,19).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475039&req=5

Figure 3: Preferential distribution of 3 novel D5D fatty acids among the liver phospholipid fractions of D6KO mice across dietary treatment groups. A) Distribution of 20:3 (Δ7,11,14); B) distribution of 20:4 (Δ7,11,14,17); C) distribution of 22:4 (Δ9,13,16,19).
Mentions: Based on previously published results [17], three peaks corresponding to three Δ-5 desaturase (D5D) derived fatty acids [20:3n6 (Δ7, 11, 14), 20:4n3 (Δ7, 11, 14, 17) and 22:4n3 (Δ9, 13, 16, 19)] were found in the liver PL fractions of D6KO mice fed LA-rich safflower oil (SF) and LA+ALA-enriched soybean oil (SO) diets (Figure 2; Figure 3). These three fatty acids were absent from all three experimental diets, and were also absent in the chromatographs of WT SF and SO fed mice. All three novel fatty acids were found to be differentially distributed among the six PL fractions (PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine; PI, phosphatidylinositol; SM, sphingomyelin; Lyso-PC, lyso-phosphatidylcholine). The PI fraction contained the highest percentage of 20:3n6 (Δ7, 11, 14) (SO =23.5 + 4.4%; SF = 30.6 + 1.6%) followed by the PS (17.7 + 1.6%), PE (11.7 + 1.7%), SM (8.4 + 3.2%), Lyso-PC (4.8 + 1.0%), and PC factions (4.1 + 0.6%) in SO-fed D6KO mice; and followed by PS (20.9 + 2.2%), PE (13.4 + 0.7%), PC (5.4 + 0.4%), SM (5.0 + 3.7%), and Lyso-PC fractions (4.0 + 1.7%) in SF-fed D6KO mice (Figure 3A). In the PI fraction of D6KO mice fed SF, 20:3n6 (Δ7, 11, 14) comprised almost a third of all fatty acids, and in the PI fraction of SO-fed D6KO mice, this novel fatty acid accounted for almost a fourth of total fatty acids. 20:4n3 (Δ7, 11, 14, 17) and 22:4n3 (Δ9, 13, 16, 19) were also selectively distributed across PL fractions, with the highest levels (relative to total fatty acids) found in PE, PI and PS fractions (Figure 3B,C).

Bottom Line: Growing evidence suggests that individual PUFA may have independent effects in health and disease.Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice.Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.

ABSTRACT

Background: Polyunsaturated fatty acids (PUFA) have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA, linoleic acid (LA) and α-linolenic acid (ALA), have been difficult to discern from the actions of their highly unsaturated fatty acid (HUFA) downstream metabolites. This issue has recently been addressed through the development of the Δ-6 desaturase knock out (D6KO) mouse, which lacks the rate limiting Δ-6 desaturase enzyme and therefore cannot metabolize LA or ALA. However, a potential confounder in this model is the production of novel Δ-5 desaturase (D5D) derived fatty acids when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid.

Objective: The aim of the present study was to characterize how the D6KO model differentially responds to diets containing the essential n-6 and n-3 PUFA, and whether the direct provision of downstream HUFA can rescue the phenotype and prevent the production of D5D fatty acids.

Methodology: Liver and serum phospholipid (PL) fatty acid composition was examined in D6KO and wild type mice fed i) 10% safflower oil diet (SF, LA rich) ii) 10% soy diet (SO, LA+ALA) or iii) 3% menhaden oil +7% SF diet (MD, HUFA rich) for 28 days (n = 3-7/group).

Results: Novel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice.

Conclusions: Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

Show MeSH
Related in: MedlinePlus