Decreased Phospholipid Remodelling May Increase DHA Bioavailability in Maternal Blood During Pregnancy
Notice bibliographique
Résumé
Background Docosahexaenoic acid (DHA) increases in maternal blood during pregnancy. While increases in DHA synthesis during pregnancy have been documented, preliminary lipidomic analyses show that plasma palmitoyldocosahexaenoyl phosphatidylcholine (16:0/DHA‐PC) is responsible for most of this increase. Objective To examine the mRNA expression of genes involved in Lands' fatty acyl remodeling cycle, PC synthesis, and lipoprotein synthesis to determine mechanisms responsible for increased maternal mobilization of 16:0/DHA‐PC into plasma during pregnancy. Methods The effect of pregnancy was examined in Sprague Dawley rats. Time points included a non‐pregnant baseline, day 15 and day 20 of pregnancy, and day‐7 postpartum (n=6 for each group). Rats were sacrificed by exsanguination following anesthesia, after an overnight fast. Tissues were collected, flash frozen in liquid nitrogen and stored in −80ºC. The mRNA was extracted from liver samples and cDNA was prepared. RT‐qPCR was performed using SYBR Green. For Lands' cycle, LPCAT 1–4, and PLA 2 G IVa, V, VI, X, XV, XVI, and DHA specific ACSL 3 and 6 were examined. For PC synthesis, GPAT 1,3,4, and AGPAT 1,2,4 and 8 were examined. Lipoprotein synthesis was examined by looking at mRNA expression of assembly proteins, ARFRP1, PPARP α, SREBF1, ABCA1, MTTP, and PLTP and apolipoproteins A1, A2, A4, A5, B, and E. Data is expressed relative to 18S as a control, with one‐way ANOVA coupled with posthoc testing to indicate significance. Results Genes involved in the Lands' cycle demonstrated the most change with pregnancy. PLA 2 GXV mRNA expression at day 20 of pregnancy was reduced by 56% as compared with baseline (p<0.05). At day‐7 post‐partum PLA 2 GXV increased by 401% compared with day 20 (p<0.05). PLA 2 GV and GXVI displayed similar but not as dramatic mRNA expression patterns, with only the PLA 2 GXVI change being significant. ACSL 3 was upregulated by 98% at day 15 compared with baseline and maintained that level expression through day 20 (P<0.05). ACSL6 expression was 93% lower at the end of pregnancy (day 20) compared with baseline and then returned to baseline levels postpartum (P<0.05). For PC synthesis, AGPAT2 expression was reduced by 52% as compared with baseline (p<0.05) and then increased by 218% at day‐7 postpartum compared with day 20. For lipoprotein synthesis, ApoA1 expression increased during pregnancy with a slight decrease postpartum, and ARFRP1 decreased during pregnancy with slight increase postpartum. PPARPα and MTTP were increased at postpartum (P<0.05). No other mRNA expression changes were observed. Conclusions The decreased expression of PLA 2 GXV and AGPAT2 suggest that remodeling of PC is decreased during pregnancy which may cause increased 16:0/DHA‐PC in maternal plasma during pregnancy. There is prior evidence that PC synthesized from phosphatidylethanolamine undergoes remodeling that decreases DHA content under normal physiological conditions. This decreased remodeling may be an appropriate adaptive mechanism during pregnancy to mobilize DHA to meet fetal demand. Support or Funding Information This work was supported by a Natural Sciences and Engineering Research Council (NSERC) Discovery grant (327149, to K.D.S), and an NSERC master's scholarship to A.C. K.D.S. is also supported by a Canada Research Chair in Nutritional Lipidomics.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».