Limits...
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.

Show MeSH

Related in: MedlinePlus

A) The normal n-6 and n-3 fatty acid metabolic pathway. B) In the absence of Δ6 desaturase, Δ5 desaturase and elongases metabolize LA and ALA to produce 3 novel fatty acids: 20:3(Δ7, 11, 14); 20:4(Δ7, 11, 14, 17), and 22:4(Δ9, 13, 16, 19).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3475039&req=5

Figure 1: A) The normal n-6 and n-3 fatty acid metabolic pathway. B) In the absence of Δ6 desaturase, Δ5 desaturase and elongases metabolize LA and ALA to produce 3 novel fatty acids: 20:3(Δ7, 11, 14); 20:4(Δ7, 11, 14, 17), and 22:4(Δ9, 13, 16, 19).

Mentions: This hurdle has recently been addressed with the development of the novel Δ-6 desaturase knock out (D6KO) mouse [16,17]. The homozygous D6KO mouse lacks a functional copy of the FADS2 gene, and is therefore unable to produce the D6D protein (Figure 1). This renders the D6KO mouse completely deficient in EPA/DHA/AA if these HUFA are not provided in the diet, since no alternative pathway for the production of these long chain fatty acids exists.


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)

A) The normal n-6 and n-3 fatty acid metabolic pathway. B) In the absence of Δ6 desaturase, Δ5 desaturase and elongases metabolize LA and ALA to produce 3 novel fatty acids: 20:3(Δ7, 11, 14); 20:4(Δ7, 11, 14, 17), and 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 1: A) The normal n-6 and n-3 fatty acid metabolic pathway. B) In the absence of Δ6 desaturase, Δ5 desaturase and elongases metabolize LA and ALA to produce 3 novel fatty acids: 20:3(Δ7, 11, 14); 20:4(Δ7, 11, 14, 17), and 22:4(Δ9, 13, 16, 19).
Mentions: This hurdle has recently been addressed with the development of the novel Δ-6 desaturase knock out (D6KO) mouse [16,17]. The homozygous D6KO mouse lacks a functional copy of the FADS2 gene, and is therefore unable to produce the D6D protein (Figure 1). This renders the D6KO mouse completely deficient in EPA/DHA/AA if these HUFA are not provided in the diet, since no alternative pathway for the production of these long chain fatty acids exists.

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