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

Alan Chalil,Alex P Kitson,Juan J Aristizabal Henao,Kristin A Marks,Jason L Elzinga,Daniel M.E Lamontagne-Kam,Daniel Chalil,Flavia Badoud,David M Mutch,Ken D Stark

doi:10.1194/jlr.m080309

Abstract

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.

Highlights

IntroductionMaternal plasma DHA increases, but the mechanism is not fully understood
This is the most comprehensive report of the fatty acid composition of the lipid classes of plasma and liver throughout pregnancy to date and allowed us to perform more targeted lipidomic assessment to determine that 16:0/DHA PC is the specific lipid responsible for most of the DHA increases in liver and plasma during pregnancy
Dietary intake was monitored and targeted protein assays were used to examine pathways related to DHA biosynthesis

Summary

Introduction

Maternal plasma DHA increases, but the mechanism is not fully understood. 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.—Chalil, A., A. While diet is an important predictor in determining blood levels of DHA during pregnancy, it appears that there are other mechanisms involved with increasing maternal circulating DHA [2, 6, 7, 10, 11]. In maternal plasma during pregnancy, there appears to be a distinct shift toward increased DHA and decreased EPA (20:5n-3) [6], suggesting additional selectivity for DHA in synthesis and/or mobilization.

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