Descomps B, Rodriguez A
Laboratoire de Biologie et Biochimie des Lipides, Université de Montpellier I.
C R Seances Soc Biol Fil. 1995;189(5):781-96.
Previous studies in our laboratory have shown that in fetal plasma arachidonic (AA) and docosahexaenoic acid (DHA) levels are higher (about two fold) than in maternal plasma whereas the reverse situation was observed for the levels of their C18 precursors linoleic acid (AL) and alpha-linolenic acid (AAL) (13). This paradoxical situation raises the questions of the origin of the long chain polyunsaturated fatty acids (PUFAs) and of the ability of fetal liver to desaturate and elongate C18 precursors since placenta was shown not to be able to desaturate fatty acids. This question should be answered for the rationale of formula feeding supplementation either with long chain PUFAs or with their C18 precursors. Three experimental approaches can contribute to elucidate this dilemna: nutritional studies with formula supplementation, investigations on hepatic enzymes in vitro, in vivo experiments using stable isotopes. Supplementation of formulas with AAL in precise conditions (AL/AAL ratio: 6.4/1 and AL intake: 4.95% of total energetic supply) was done in a multicentric study including 88 premature newborns (32 weeks post conceptional age) for five weeks. The plasma phospholipid and red blood cell DHA status was found to be closer to human milk feeding than with standard formula feeding and most of the n-6 pathway was preserved. The data suggests that in premature newborns a significant conversion of AAL into DHA is possible provided an equilibrium is respected between AL and AAL supplies. This conversion is confirmed both by in vitro and in vivo studies: in fetal livers (obtained from therapeutic abortion) significant delta 6 and delta 5 desaturase activities were measured by a radiochemical method using reverse phase HPLC separation of [1-14C] labelled substrates and products in the n-6 and in the n-3 series. Substrate inhibition was observed especially at delta 5 desaturation and the maximum velocities were relatively limited mainly in the n-6 pathway which was slower than in the n-3 serie. These data are in agreement with recent preliminary data obtained in different laboratories with stable isotopes in vivo but in infants born in term: experiments using either 13C or deuterium labelled fatty acids concluded to the conversion of C18 essential fatty acids into AA and DHA justifying (AAL) formula supplementation for sustaining DHA status in preterm newborns.
我们实验室之前的研究表明，胎儿血浆中花生四烯酸（AA）和二十二碳六烯酸（DHA）的水平比母体血浆中的水平更高（约两倍），而它们的C18前体亚油酸（AL）和α-亚麻酸（AAL）的水平则呈现相反的情况（13）。这种矛盾的情况引发了关于长链多不饱和脂肪酸（PUFA）的来源以及胎儿肝脏使C18前体去饱和和延长的能力的问题，因为胎盘已被证明无法使脂肪酸去饱和。对于配方奶补充长链PUFA或其C18前体的基本原理，这个问题应该得到解答。三种实验方法有助于阐明这一困境：配方奶补充的营养研究、体外肝脏酶的研究、使用稳定同位素的体内实验。在一项多中心研究中，在精确条件下（AL/AAL比例：6.4/1，AL摄入量：总能量供应的4.95%）用AAL补充配方奶，该研究包括88名早产新生儿（孕龄32周），为期五周。发现血浆磷脂和红细胞DHA状态与母乳喂养比与标准配方奶喂养更接近，并且大部分n-6途径得以保留。数据表明，在早产新生儿中，只要AL和AAL供应之间保持平衡，AAL就有可能大量转化为DHA。这种转化在体外和体内研究中都得到了证实：在胎儿肝脏（从治疗性流产获得）中，通过使用反相HPLC分离n-6和n-3系列中[1-14C]标记的底物和产物的放射化学方法，测量了显著的δ6和δ5去饱和酶活性。观察到底物抑制，特别是在δ5去饱和时，最大速度相对有限，主要在n-6途径中，该途径比n-3系列慢。这些数据与最近在不同实验室使用稳定同位素在足月出生的婴儿体内获得的初步数据一致：使用13C或氘标记脂肪酸的实验得出C18必需脂肪酸转化为AA和DHA的结论，证明补充（AAL）配方奶以维持早产新生儿的DHA状态是合理的。
