Sex differences in hippocampal-dependent memory and the hippocampal lipidome in adolescent rats raised on diets with or without DHA.

Recent studies suggest the effects of DHA supplementation on human memory may differ between females and males during infancy, adolescence, and early adulthood, but the underlying mechanisms are not clear. As a result, this study sought to examine the spatial memory and brain lipidomic profiles in female and male adolescent rats with or without a DHA-enriched diet that began perinatally with the supplementation of dams. Spatial learning and memory were examined in adolescent rats using the Morris Water Maze beginning at 6 weeks of age and animals were sacrificed at 7 weeks of age to permit isolation of brain tissue and blood samples. Behavioral testing showed that there was a significant diet x sex interaction for two key measures of spatial memory (distance to zone and time spent in the correct quadrant during the probe test), with female rats benefiting the most from DHA supplementation. Lipidomic analyses suggest levels of arachidonic acid (ARA) and n-6 docosapentaenoic acid (DPA) containing phospholipid species were lower in the hippocampus of DHA supplemented compared with control animals, and principal component analyses revealed a potential dietary treatment effect for hippocampal PUFA. Females fed DHA had slightly more PE P-18:0_22:6 and maintained levels of PE 18:0_20:4 in the hippocampus in contrast with males fed DHA. Understanding how DHA supplementation during the perinatal and adolescent periods changes cognitive function in a sex-specific manner has important implications for determining the dietary requirements of DHA. This study adds to previous work highlighting the importance of DHA for spatial memory and provides evidence that further research needs to consider how DHA supplementation can cause sex-specific changes.

Concentrations of docosahexaenoic acid are reduced in maternal liver, adipose, and heart in rats fed high-fat diets without docosahexaenoic acid throughout pregnancy.

Fetal accretion for DHA is high during late pregnancy due to the brain growth spurt. Prior evidence suggests that DHA is mobilized from maternal liver and adipose to meet fetal accretion and physiological requirements. However, changes in the DHA levels of various maternal tissues throughout pregnancy and into lactation of mothers on diets with and without dietary DHA, and with a background dietary fatty acid profile that resembles human intake has not been examined. Sprague Dawley rats were fed a total western diet with (TWD + ) or without DHA (TWD-) along with a commercial rodent chow control (Chow) throughout pregnancy and postpartum. The fatty acid compositions of adipose, brain, heart, liver, erythrocytes, and plasma were determined before pregnancy, at 15 and 20 days of pregnancy, and 7 days postpartum. The placenta, fetuses, and pups were also examined when available. Maternal DHA concentrations were increased in plasma at 20 days pregnancy in all the diets with TWD + > Chow > TWD-. Maternal DHA concentrations in the TWD- group were lower in adipose throughout pregnancy as compared with the other diets. At postpartum, DHA concentrations decreased below baseline levels in the heart of the TWD- and Chow dams and the liver of the TWD- dams. Whole body DHA concentrations of the fetuses did not differ but there was evidence of decreased DHA in the whole body and tissues of the TWD- and Chow 7d old pups. In conclusion, it appears that in this rodent model of pregnancy, maternal adaptations were made to meet fetal DHA requirements, but they may compromise maternal DHA status and the ability to deliver DHA during lactation.

PEMT, Δ6 desaturase, and palmitoyldocosahexaenoyl phosphatidylcholine are increased in rats during pregnancy.

DHA is important for fetal neurodevelopment. During pregnancy, maternal plasma DHA increases, but the mechanism is not fully understood. Using rats fed a fixed-formula diet (DHA as 0.07% total energy), plasma and liver were collected for fatty acid profiling before pregnancy, at 15 and 20 days of pregnancy, and 7 days postpartum. Phosphatidylethanolamine methyltransferase (PEMT) and enzymes involved in PUFA synthesis were examined in liver. Ad hoc transcriptomic and lipidomic analyses were also performed. With pregnancy, DHA increased in liver and plasma lipids, with a large increase in plasma DHA between day 15 and day 20 that was mainly attributed to an increase in 16:0/DHA phosphatidylcholine (PC) in liver (2.6-fold) and plasma (3.9-fold). Increased protein levels of Δ6 desaturase (FADS2) and PEMT at day 20 and increased Pemt expression and PEMT activity at day 15 suggest that during pregnancy, both DHA synthesis and 16:0/DHA PC synthesis are upregulated. Transcriptomic analysis revealed minor changes in the expression of genes related to phospholipid synthesis, but little insight on DHA metabolism. Hepatic PEMT appears to be the mechanism for increased plasma 16:0/DHA PC, which is supported by increased DHA biosynthesis based on increased FADS2 protein levels.