Two weeks of docosahexaenoic acid (DHA) supplementation increases synthesis-secretion kinetics of n-3 polyunsaturated fatty acids compared to 8 weeks of DHA supplementation.

Docosahexaenoic acid (DHA, 22:6n-3) must be consumed in the diet or synthesized from n-3 polyunsaturated fatty acid (PUFA) precursors. However, the effect of dietary DHA on the metabolic pathway is not fully understood. Presently, 21-day-old Long Evans rats were weaned onto one of four dietary protocols: 1) 8 weeks of 2% ALA (ALA), 2) 6 weeks ALA followed by 2 weeks of 2% ALA + 2% DHA (DHA), 3) 4 weeks ALA followed by 4 weeks DHA and 4) 8 weeks of DHA. After the feeding period, 2H5-ALA and 13C20-eicosapentaenoic acid (EPA, 20:5n-3) were co-infused and blood was collected over 3 h for determination of whole-body synthesis-secretion kinetics. The synthesis-secretion coefficient (ml/min, means ± SEM) for EPA (0.238±0.104 vs. 0.021±0.001) and DPAn-3 (0.194±0.060 vs. 0.020±0.008) synthesis from plasma unesterified ALA, and DPAn-3 from plasma unesterified EPA (2.04±0.89 vs. 0.163±0.025) were higher (P<.05) after 2 weeks compared to 8 weeks of DHA feeding. The daily synthesis-secretion rate (nmol/d) of DHA from EPA was highest after 4 weeks of DHA feeding (843±409) compared to no DHA (70±22). Liver gene expression of ELOVL2 and FADS2 were lower (P<.05) after 4 vs. 8 weeks of DHA. Higher synthesis-secretion kinetics after 2 and 4 weeks of DHA feeding suggests an increased throughput of the PUFA metabolic pathway. Furthermore, these findings may lead to novel dietary strategies to maximize DHA levels while minimizing dietary requirements.

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.