Developmental Accretion of Docosahexaenoic Acid Is Independent of Fatty Acid Transporter Expression in Brain and Lung Tissues of C57BL/6 and Fat1 Mice

Abstract

Background: Developmental expression of fatty acid transporters and their role in polyunsaturated fatty acid concentrations in the postnatal period have not been evaluated.

Objective: We hypothesized that transporter expression is developmentally regulated, tissue-specific, and that expression can modulate fatty acid accretion independently of diet.

Methods: Brain and lung transporter expression were quantified in C57BL/6 wild-type (WT) and Fat1 mice. Pups were dam-fed until day 21. Dams were fed AIN-76A 10% corn oil to represent a typical North American/European diet. After weaning, mice were fed the same diet as dams. Gene expression of Fatp1, Fatp4, Fabp5, and Fat/cd36 was quantified by quantitative reverse transcriptase-polymerase chain reaction. Fatty acid concentrations were measured by GC-MS.

Results: Brain docosahexaenoic acid (DHA) concentrations increased from day 3 to day 28 in both genotypes, with higher concentrations at days 3 and 14 in Fat1 than in WT mice [median (IQR)]: 10.7 (10.6-11.2) mol% compared with 6.6 (6.4-7.2) mol% and 12.5 (12.4-12.9) mol% compared with 8.9 (8.7-9.1) mol%, respectively; P < 0.05). During DHA accrual, transporter expression decreased. Fold changes in brain Fatp4, Fabp5, and Fat/cd36 were inversely correlated with fold changes in brain DHA concentrations in Fat1 relative to WT mice (ρ = -0.85, -0.75, and -0.78, respectively; P ≤ 0.001). Lung DHA concentrations were unchanged across the 3 time points for both genotypes. Despite unchanging DHA concentrations, there was increased expression of Fatp1 at days 14 and 28 (5-fold), Fatp4 at day 14 (2.3-fold), and Fabp5 at day 14 (3.8-fold) relative to day 3 in Fat1 mice. In WT mice, Fatp1 increased almost 5-fold at day 28 relative to day 3. There was no correlation between lung transporters and DHA concentrations in Fat1 relative to WT mice.

Conclusions: Development of fatty acid transporter expression in C57BL/6 WT and Fat1 mice is genotype and tissue specific. Further, postnatal accretion of brain DHA appears independent of transporter status, with tissue concentrations representing dietary contributions.

Keywords: arachidonic acid; docosahexaenoic acid; fatty acid accretion; fatty acid transporters; newborn development.

FIGURE 1

mRNA expression of fatty acid transport proteins in Fat1 and WT mice for brain (A–C) and lung (D–F) tissues on postnatal days 3, 14, and 28. (A, D) transporter expression in Fat1 mice on days 14 and 28 relative to day 3; (B, E) transporter expression in WT mice on days 14 and 28 relative to day 3; (C, F) transporter expression in Fat1 relative to WT mice at each postnatal day. Fold changes are reported as median (IQR) fold changes (n = 31; Fat1 n = 6, 6, 5, and WT n = 6, 3, and 5, for days 3, 14, and 28, respectively). Statistical significance of the change in transporter expression across time for each genotype was determined by Kruskal–Wallis test followed by pairwise comparisons adjusted by Dunn's multiple comparison test. Labeled points without a common letter are significantly different, P ˂ 0.05. Fabp5, fatty acid binding protein 5; Fat/cd36, fatty acid translocase/cluster domain 36; Fatp1, fatty acid transport protein 1; Fatp4, fatty acid transport protein 4; WT, wild-type.

FIGURE 2

Spearman rank correlation coefficients of mRNA expression of fatty acid transporters and DHA (A–D) and AA (E–H) in brain tissue. mRNA expression and fatty acid values are summarized as fold changes in Fat1 mice relative to WT littermates (n = 17). AA, arachidonic acid; Fabp5, fatty acid binding protein 5; Fat/cd36, fatty acid translocase/cluster domain 36; Fatp1, fatty acid transport protein 1; Fatp4, fatty acid transport protein 4; WT, wild-type.

FIGURE 3

Spearman rank correlation coefficients of mRNA expression of fatty acid transporters and DHA (A–D) and AA (E–H) in lung tissue. mRNA expression and fatty acid values are summarized as fold changes in Fat1 mice relative to WT littermates (n = 17). AA, arachidonic acid; Fabp5, fatty acid binding protein 5; Fat/cd36, fatty acid translocase/cluster domain 36; Fatp1, fatty acid transport protein 1; Fatp4, fatty acid transport protein 4; WT, wild-type.