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


METHODS
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.
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
Jessica
J
Monteiro
Feng-Jun
FJ
Li
Mira
M
Maclennan
Alexandra
A
Rabalski
Mohammed H
MH
Moghadasian
Manabu T
MT
Nakamura
David Wl
DW
Ma
D000818:Animals; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005395:Fish Oils / Q000008:administration & dosage*; D019787:Linoleic Acid / Q000097:blood / Q000378:metabolism*; D050602:Linoleoyl-CoA Desaturase / Q000172:deficiency* / Q000235:genetics; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010743:Phospholipids / Q000097:blood / Q000378:metabolism; D012450:Safflower Oil / Q000008:administration & dosage*; D013024:Soybean Oil / Q000008:administration & dosage*; D017962:alpha-Linolenic Acid / Q000097:blood / Q000378:metabolism*
D000090943:Delta-5 Fatty Acid Desaturase; D005395:Fish Oils; D010743:Phospholipids; D017962:alpha-Linolenic Acid; C033266:Menhaden oil; D013024:Soybean Oil; D012450:Safflower Oil; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase