Fig. 4. Effect of dietary DHA supplementation on the lipid compositions and behavior of Fads(Δ/+) mice.

a Frequency of depression-like episodes in female Fads(Δ/+) mice fed the AIN93G diet (control) and AIN93G supplemented with DHA and/or EPA. DHA supplementation significantly reduced the frequency of DEs (*P < 0.05, ^#P < 0.1, r = 0.331 and 0.315 [medium ES], U-test with Bonferroni correction following Kruskal-Wallis test). b PCA plot of Fads(Δ/+) and WT mice fed the five different diets based on brain lipidomics data (Supplementary Table 1a). A two-way ANOVA revealed a significant and large effect of genotype (P < 0.001, η² = 0.15) but not diet on the Euclidean distance between the lipid compositions of the samples measured. c, d Lipid class (c) and fatty acid (d) enrichment analyses of differentially changed brain lipids between Fads(Δ/+) mice fed AIN93G and those supplemented with DHA. The abbreviations for the lipid classes are listed in Supplementary Table 4. e OPLS-DA loading plot of the 464 brain lipids from Fads(Δ/+) mice fed AIN93G and from those supplemented with DHA. The top 1% of lipid molecules are highlighted. The comparisons of these individual lipids between diet groups are shown in Supplementary Fig. 10. f Plasma fatty acid levels in Fads(Δ/+) mice fed the AIN93G diet (AIN, n = 7) and those of mice supplemented with DHA (n = 6). In Fads(Δ/+) mice supplemented with DHA, DHA itself and its precursor metabolite, EPA, were significantly increased (***P < 0.001, d = 1.884 and 1.419 [large ES], t-test), and the major ω6 metabolite AA was reduced (**P < 0.05, d = 1.437 [large ES]). For the boxplot description, see the legend of Fig. 1c.