Dietary Phospholipid-Bound Conjugated Linoleic Acid and Docosahexaenoic Acid Incorporation Into Fetal Liver and Brain Modulates Fatty Acid and N-Acylethanolamine Profiles.

Elisabetta Murru,Gianfranca Carta,Marco Pistis,Sebastiano Banni,Michele Santoni,Rafaela Mostallino,Claudia Manca,Asgeir Saebo

doi:10.3389/fnut.2022.834066

Elisabetta Murru, Gianfranca Carta + Show 6 more

Open Access

https://doi.org/10.3389/fnut.2022.834066

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Abstract

We evaluated whether maternal intake of conjugated linoleic acid (CLA) and docosahexaenoic acid (DHA) in the phospholipid (PL) form (CLA-DHA PL) affects maternal and fetal brain and liver fatty acids (FAs) profile and the biosynthesis of FA-derived bioactive lipid mediators N-acylethanolamines (NAEs) involved in several neurophysiological functions. We fed rat dams during the first 2/3 of their pregnancy a CLA-DHA PL diet containing PL-bound 0.5% CLA and 0.2% DHA. FA and NAE profiles were analyzed in maternal and fetal liver and brain by Liquid Chromatography diode array detector (LC-DAD) and MS/MS in line. We found that CLA and DHA crossed the placenta and were readily incorporated into the fetal liver and brain. CLA metabolites were also found abundantly in fetal tissues. Changes in the FA profile induced by the CLA-DHA PL diet influenced the biosynthesis of NAE derived from arachidonic acid (ARA; N-arachidonoylethanolamine, AEA) and from DHA (N-docosahexaenoylethanolamine, DHEA). The latter has been previously shown to promote synaptogenesis and neuritogenesis. The reduced tissue n6/n3 ratio was associated to a significant decrease of AEA levels in the fetal and maternal liver and an increase of DHEA in the fetal and maternal liver and in the fetal brain. Maternal dietary CLA-DHA PL by promptly modifying fetal brain FA metabolism, and thereby, increasing DHEA, might represent an effective nutritional strategy to promote neurite growth and synaptogenesis and protect the offspring from neurological and psychiatric disorders with neuroinflammatory and neurodegenerative basis during the critical prenatal period.

Highlights

The fat composition in the fetus is of major importance, as the intrauterine requirement of n6 and n3 polyunsaturated fatty acids (PUFAs) in the human fetus development during the last trimester and the early weeks of life is 400 and 50 mg/kg/day, respectively [1]
Our data showed that conjugated linoleic acid (CLA) and docosahexaenoic acid (DHA) in PL form crossed the placenta and were readily incorporated into the maternal and fetal liver and brain of fetuses, but not into dams’ brain, to previous studies where short-term dietary supplementation with CLA or DHA was hardly incorporated into adult rat brain [56, 58]
We observed a significant positive correlation between circulating levels of maternal CLA and its CD18:3 metabolite with the respective levels in fetal liver (R = 0.72; p ≤ 0.03 and 0.83 p ≤ 0.01, respectively), while we did not find any significant correlation with CD16:2 metabolite, which is produced by CLA peroxisomal beta-oxidation

Summary

Introduction

The fat composition in the fetus is of major importance, as the intrauterine requirement of n6 and n3 polyunsaturated fatty acids (PUFAs) in the human fetus development during the last trimester and the early weeks of life is 400 and 50 mg/kg/day, respectively [1]. A placental selectivity and high affinity for the transport of individual FA to the fetus has been reported [10–12], explaining why the concentrations of some LC-PUFA, as ARA and DHA, are greater in the fetal than maternal circulation [10, 13–15]. Haggarty et al [16] found a selective preferential placental transport of DHA with order of preference DHA > ARA > alpha linolenic acid (ALA, 18:3n3) > linoleic acid (LA, 18:2n6) [16, 17]. It was shown that incorrect nutritional management of the mother during fetal brain development might lower the threshold for neurological disorders later in life [24, 25]

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