Brain concentrations of docosahexaenoic acid in neonatal mice are independent of fatty acid transporter expression

Long chain polyunsaturated fatty acids play many essential roles in mediating inflammatory reactions, brain myelination, and cognitive function.

Docosahexaenoic acid (DHA) can be synthesized from the essential w-3 fatty acid a-linolenic acid or derived from the diet as DHA.  The synthesis of DHA includes elongation of the carbon chain and desaturation.  Genetic variability in the desaturase genes has been postulated as explaining part of the variability in tissue DHA levels, but the evidence available does not explain all of the associations.

Another source of variability in tissue levels of DHA may be attributed to the expression of fatty acid transporters.  Differences in transporter expression may be both developmentally regulated and tissue dependent, which may explain tissue-specific accretion of DHA in newborns.  Yakah and colleagues explored this hypothesis in mice and report their results in the October 2019 issue of The Journal of Nutrition.

The experiment used wild-type C57BL/6 mice, which when provided a diet rich in w-6 fatty acids are a model of westernized diets, and Fat1 mice, which are able to synthesize w-3 fatty acids as they express the Fat1 desaturase gene.  Brain and lung expression of fatty acid transporters were measured in offspring from dams consuming a diet containing 10% corn oil.  The pups were weaned at day 21 and at that time received the same diet as the dam.  Samples were collected from the pups at days 3, 14 and 28 to determine gene expression and fatty acid concentrations.

Both genotypes had increasing concentrations of DHA in the brain from day 3 to 28 in the face of decreasing expression of fatty acid transporters.  At days 3 and 14, the concentrations of DHA were higher in the Fat1 mice than in the wild-type mice.  Lung concentrations of DHA were not different at the 3 time points for both genotypes, even though the expression of some fatty acid transporters were elevated in the mice. 

These observations led the authors to conclude that the temporal pattern of fatty acid transporter expression is genotype and tissue specific. Importantly, the concentrations of DHA in the brain appears to be diet-dependent, and independent of fatty acid transporter expression. In a commentary on this article, Mazzocchi and Agostoni, agree that the data presented by Yakah and colleagues indicate that diet may be the major determinant of w-3 long chain fatty acids in the brain throughout development. 

References:

Yakah W, Singh P, Perides G, Brown J, Freedman SD, Martin CR.  Developmental accretion of docosahexaenoic acid is independent of fatty acid transporter expression in brain and lung tissues of C57BL/6 and Fat1 mice. The Journal of Nutrition, Volume 149, Issue 10, October 2019, Pages 1724–1731, https://doi.org/10.1093/jn/nxz074

Mazzocchi A, Agostoni C.  Long-chain w-3 polyunsaturated fatty acids:  Do genetic steps match metabolic needs? The Journal of Nutrition, Volume 149, Issue 10, October 2019, Pages 1690–1691, https://doi.org/10.1093/jn/nxz160

Because critical tissues levels, such as those in the brain, appear to be dependent on diet content of the preformed long chain w-3 fatty acids, Mazzocchi and Agostoni suggest the need for further work to focus on digestion and absorption of these fatty acids, and determine whether there may be temporal differences in those processes.