Evidence of multiple hepatic mechanisms to mobilize docosahexaenoic acid into dam plasma during pregnancy in chow-fed sprague dawley rats

Abstract

Fetal brain growth requires considerable amounts of docosahexaenoic acid (DHA) during late pregnancy that is associated with increased maternal/dam plasma levels of PC 16:0_22:6 (palmitoyl docosahexaenoyl phosphatidylcholine). While biosynthesis of DHA during pregnancy is upregulated, the mechanisms responsible for the incorporation of dam DHA into PC 16:0_22:6 are not understood. The present study used a discovery approach combining untargeted lipidomics of plasma and liver (n = 3/group) with semi-targeted qPCR of hepatic gene products (n = 6/group) to identify metabolic pathways related to DHA metabolism, with a hypothesis that an upregulated acyltransferase involved in PC remodeling would be identified. Sprague Dawley rats were fed a commercial rodent chow throughout the study and samples were collected before pregnancy (baseline), at 15 and 20 days of pregnancy, and 7 days postpartum. Plasma and hepatic PC 16:0_22:6 was significantly increased (by 79% and 194%, respectively) at day 20 of pregnancy. An increase in hepatic DG (diacylglycerol) 16:0_22:6 (by 243%) and significant decreases in Pla2G15 (0.4-fold) and Pla2G16 (0.6-fold) at day 20 of pregnancy, no changes in Lpcat1-4, and an abundant pool of hepatic pool PE (phosphatidylethanolamine) 16:0_22:6 suggest that plasma PC 16:0_22:6 is not being produced by fatty acyl remodeling during pregnancy. The increase in plasma PC 16:0_22:6 during pregnancy appears to be due to an increase in de novo synthesis of PC and both the CDP-choline and phosphatidylcholine methyltransferase pathways are implicated. There was also evidence suggesting channeling of DHA into PC and lipoprotein assembly may be occurring. Targeted research is necessary to confirm these findings, but the results of this study indicate metabolic adaptions to enable maternal/dam resiliency towards meeting the fetal/pup demand for DHA during pregnancy.

Keywords: Docosahexaenoic acid; Gene expression; Lipidomics; Liver; Maternal; Omega-3; PC 16:0_22:6; Plasma; Postpartum; Pregnancy; Tandem mass spectrometry; qPCR.