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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Abbreviations
- ANOV:
-
analysis of variance
- EFA:
-
essential fatty acids
- FA:
-
fatty acids
- GLC:
-
gas-liquid chromatography
- GLM:
-
general linear model
- MUFA:
-
monounsaturated fatty acids
- PC:
-
phosphatidylcholine
- PE:
-
phosphatidylethanolamine
- PUFA:
-
polyunsaturated fatty acids
- SAS:
-
Statistical Analysis Systems
- SFA:
-
saturated fatty acids
References
Sinclair, A.J. (1975)Proc. Nutr. Soc. 34, 287–291.
Breckenridge, W.C., Morgan, I.G., Zanetta, J.P., and Vincendon, G. (1970)Biochim. Biophys. Acta 320, 681–686.
Anderson, R.E., Benolken, R.M., Dudley, P.A., Landis, D.J., and Wheeler, T.G. (1974)Exp. Eye. Res. 18, 205–213.
Tinoco, J., Miljanich, P., and Medwadowski, B. (1977)Biochim. Biophys. Acta 486, 575–578.
Sinclair A.J., and Crawford, M.A. (1972)J. Neurochem. 19, 1753–1758.
Clandinin, M.T., Chappell, J.E., Leong, S., Heim, T., Swyer, P.R., and Chance, G.W. (1980)Early Hum. Dev. 4, 121–129.
Crawford, M.A., Hassam, A.G., and Stevens, P.A. (1982)Prog. Lipid Res. 20, 31–40.
Sprecher, H. (1981)Prog. Lipid Res. 20, 13–22.
Cook, H.W. (1978)J. Neurochem. 30, 1327–1334.
Sanders, T.A.B., and Rana, S.K. (1987)Ann. Nutr. Metab. 31, 349–353.
Bazan, N.G., and Scott, B.L. (1990)Upsala J. Med. Sci., Suppl. 48, 97–107.
Anderson, G.J., and Connor, W.E. (1988)Lipids 23, 286–290.
Anderson, G.J., Connor, W.E., and Corliss, J.D. (1990)Pediatr. Res. 27, 89–97.
Bourre, J.M., Francois, M., Youyou, A., Dumont, O., Piciotti, M., Pascal, G., and Durand, G. (1989)J. Nutr. 119, 1880–1892.
Mohrhauer, H., and Holman, R.T. (1963)J. Neurochem. 10, 523–530.
Anding, R.H., and Hwang, D.H. (1986)Lipids 21, 697–701.
Dyer, J.R., and Greenwood, C.E. (1991)J. Neurochem. 56, 1921–1931.
Bourre, J.M., Bonneil, M., Dumont, O., Piciotti, M., Nalbone, G., and Lafont, H. (1988)Biochim. Biophys. Acta 969, 458–461.
Bourre, J.M., Bonneil, M., Dumont, O., Piciotti, M., Calaf, R., Portugal, H., Nalbone, G., and Lafonte, H. (1990)Biochim. Biophys. Acta 1043, 149–152.
Carlson, S.E., and Salem Jr. N. (1991) inHealth Effects of ω3 Polyunsaturated Fatty Acids in Seafoods (Simopoulos, A.P., Kifer, R.R., Martin, R.E., and Barlow, S.M., eds.) Vol. 8, pp. 74–86, Karger, Basel.
Carroll, K.K. (1989)J. Nutr. 119, 1810–1813.
Hassam, A.G., Sinclair, A.J., and Crawford, M.A. (1975)Lipids 10, 417–420.
Wainwright, P.E., Huang, Y.S., Bulman-Fleming, B., Mills, D.E., Redden, P., and McCutcheon, D. (1991)Lipids 26, 37–45.
Wainwright, P.E., Ward, G.R., Winfield, D., Huang, Y.S., Mills, D.E., and Ward, R.P., and McCutcheon, D. (1990)Alcohol. Clin. Exp. Res. 14, 405–412.
Wainwrigh, P.E., Huang, Y.S., Simmons, V., Mills, D.E., Ward, R.P., Ward, G.W., Winfield, D., and McCutcheon, D. (1990)Alchol. Clin. Exp. Res. 14, 413–420.
Huang, Y.S., Wainwright, P.E., Redden, P.R., Mills, D.E., Bulman-Fleming, B., and Horrobin, D.F. (1992)Lipids 27, 104–110.
Mills, D., Ward, R.P., and Huang, Y.S. (1990)J. Nutr. 120, 431–435.
Bligh, E.G., and Dyer, W.J. (1959)Can. J. Biochem. Physiol. 37, 911–917.
Redden, P.R., and Huang, Y.S. (1991)J. Chromatogr. 567, 21–27.
Lands, W.E.M., Morris, A., and Libelt, B. (1990)Lipids 25, 505–516.
Bourre, J.M., Piciotti, M., Dumont, O., Pascal, G., and Durand, G. (1990)Lipids 25, 465–472.
Garg, M.L., Sebokova, E., Thomson, A.B.R., and Clandinin M.T. (1988)Biochem. J. 249, 351–356.
Garg, M.L., Thomson, A.B.R., and Clandinin M.T. (1988)J. Nutr. 118, 661–668.
Brenner, R.R. (1981)Prog. Lipid Res. 20, 41–47.
Tinoco, J., Babcock, R., Hincenbergs, I., Medwadowski, B., and Miljanich, P. (1978)Lipids 13, 6–17.
Crawford, M.A. (1986)Prog. Lipids Res. 25, 615–618.
Nouvelot, A., Bourre, J.M., Sezille, G., Dewailly, P., and Jaillard, J. (1983)Ann. Nutr. Metab. 27, 173–181.
Yeh, Y.-Y., Winters, B.L., and Yeh, S.-M. (1990)J. Nutr. 120, 436–443.
Willis, A.L. (1981)Prog. Lipids Res. 20, 839–850.
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Wainwright, P.E., Huang, Y.S., Bulman-Fleming, B. et al. 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. Lipids 27, 98–103 (1992). https://doi.org/10.1007/BF02535807
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DOI: https://doi.org/10.1007/BF02535807