The Effects of dietary n?3/n?6 ratio on brain development in the mouse: a dose response study with long-chain n?3 fatty acids |
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Authors: | P E Wainwright Y S Huang B Bulman-Fleming D Dalby D E Mills P Redden D McCutcheon |
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Affiliation: | (1) Department of Health Studies, University of Waterloo, N2L 3G1 Waterloo, Ontario, Canada;(2) Efamol Research Institute, B4N 4H8 Kentville, Nova Scotia, Canada |
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Abstract: | This study examines the effects of the ratio of n−3/n−6 fatty acids (FA) on brain development in mice when longchain n−3 FA
are supplied in the diet. From conception until 12 days after birth, B6D2F1 mice were fed liquid diets, each providing 10% of energy from olive oil, and a further 10% from different combinations of
free FA concentrates derived from safflower oil (18∶2n−6), and fish oil (20∶5n−3 and 22∶6n−3). The range of dietary n−3/n−6
ratios was 0,025, 0.5, 1.0, 2.0, and 4.0, with an n−6 content of greater than 1.5% of energy in all diets, and similar levels
of total polyunsaturated fatty acids (PUFA). In an additional group of ratio 0.5, 18∶2n−6 was partially replaced by its δ6
desaturation product, 18∶3n−6. Biochemical analyses were conducted on 12-day-old pup brains, as well as on samples of maternal
milk. No obvious effects on overall pup growth and development were observed, apart from a smaller litter size at ratio 1.
Co-variance analysis indicated that increasing the n−3/n−6 ratio was associated with slightly smaller brains, relative to
body weight. We found that 18∶2n−6 and 20∶5n−3 were the predominant n−6 and n−3 FA in the milk; in the brain these were 20∶4n−6
and 22∶6n−3, respectively. Increasing dietary n−3/n−6 ratios generally resulted in an increase in n−3 FA, with a corresponding
decrease in n−6 FA. The n−3/n−6 ratio of the milk lipids showed a strong linear relationship with the diet, but in the brain
the rate of increase tended to decrease beyond 0.5 (phosphatidylcholine, PC) and 0.25 (phosphatidylethanolamine, PE), such
that there was a significant quadratic contribution to the relationship. The partial replacement of dietary 18∶2n−6 with 18∶3n−6
raised levels of 20∶4n−6 in milk, brain PC, and brain PE. These results indicate that the n−3/n−6 ratio of the phospholipids
in the developing mouse brain responds maximally to maternal dietary long-chain n−3/n−6 ratios of between 0.25 and 0.5. |
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