Su H M, Huang M C, Saad N M, Nathanielsz P W, Brenna J T
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
J Lipid Res. 2001 Apr;42(4):581-6.
Using [13C]-tracers and direct fetal doses, we show for the first time that the fetal primate converts alpha-linolenic acid (18:3) to docosahexaenoic acid (22:6) in vivo, and we estimate the relative bioefficacy of the two substrates for brain 22:6 accretion. Pregnant female baboons consumed a diet free of long chain polyunsaturates (LCP), with n-6/n-3 ratio of 10/1. In the third trimester of pregnancy (normal gestation = 182 days), they were instrumented with chronic indwelling catheters in the maternal femoral artery and the fetal jugular artery. Doses of either [U-13C]-18:3 (18:3*, n = 3) or [U-13C]-22:6 (22:6*, n = 2) were administered directly to the fetus. Blood was collected from fetus and mother, and the fetus was taken by cesarean section when electromyographic activity indicated that parturition was imminent. Fetal liver, brain, retina, and retinal pigment epithelium (RPE) were collected, and (13)C fatty acids determined. In 18:3*- dosed animals, labeled n-3 LCP were detected in fetal plasma at 1 day post-dose and peaked at 2;-3 days; brain 22:6* was constant at 3, 5, and 9 days post-dose, at 0.57 +/- 0.03 percent of dose (%Dose). In 22:6*- dosed animals, brain 22:6* was similar at 3 and 9 days post-dose (4.64 +/- 0.43%Dose). From these data, we estimate that preformed 22:6 in the fetal bloodstream is 8-fold more efficacious for brain 22:6 accretion than is 18:3. Retina 22:6* was stable at about 0.0008%Dose from 3 to 9 days in 18:3-dosed animals, but RPE 22:6* dropped over the period; brain results were consistent with these observations. Liver showed about 0.5%Dose in 22:6* and in intermediary n-3 fatty acid metabolites 20:5* and 22:5* at 3 days post-dose, and declined afterward. Back-transfer of labeled fatty acids to the maternal bloodstream was measurable but not sufficient to compromise the quantitative conversion data in fetuses. We conclude 1) primate fetuses have the capacity to convert 18:3 to 22:6 in vivo; 2) fetal brain 22:6* as %Dose plateaus by 3 days post-dose; 3) fetal plasma 22:6 is about 8-fold more effective as a substrate for brain 22:6 accretion compared with 18:3; and 4) the fetal liver is likely to be an important site of 18:3 to 22:6 conversion.
使用[13C]示踪剂和直接给予胎儿的剂量，我们首次证明灵长类胎儿在体内可将α-亚麻酸（18:3）转化为二十二碳六烯酸（22:6），并且我们估算了这两种底物对胎儿大脑中22:6积累的相对生物效能。怀孕的雌性狒狒食用不含长链多不饱和脂肪酸（LCP）的饮食，n-6/n-3比例为10/1。在妊娠晚期（正常妊娠期为182天），它们通过在母体股动脉和胎儿颈静脉中植入慢性留置导管来进行操作。将[U-13C]-18:3（18:3*，n = 3）或[U-13C]-22:6（22:6*，n = 2）直接给予胎儿。从胎儿和母体采集血液，当肌电图活动表明即将分娩时，通过剖宫产取出胎儿。收集胎儿的肝脏、大脑、视网膜和视网膜色素上皮（RPE），并测定（13）C脂肪酸。在给予18:3的动物中，给药后1天在胎儿血浆中检测到标记的n-3 LCP，并在2 - 3天达到峰值；给药后3、5和9天，大脑中的22:6保持恒定，为剂量的0.57±0.03%（%剂量）。在给予22:6的动物中，给药后3天和9天大脑中的22:6相似（4.64±0.43%剂量）。根据这些数据，我们估计胎儿血液中预先形成的22:6对大脑22:6积累的效能比18:3高8倍。在给予18:3的动物中，从3天到9天，视网膜中的22:6稳定在约0.0008%剂量，但在此期间RPE中的22:6下降；大脑的结果与这些观察结果一致。给药后3天，肝脏中22:6以及中间的n-3脂肪酸代谢物20:5和22:5显示约0.5%剂量，随后下降。标记脂肪酸向母体血液的反向转移是可测量的，但不足以影响胎儿中的定量转化数据。我们得出结论：1）灵长类胎儿在体内有将18:3转化为22:6的能力；2）给药后3天，胎儿大脑中22:6作为%剂量达到平台期；3）与18:3相比，胎儿血浆中的22:6作为大脑22:6积累的底物的有效性约高8倍；4）胎儿肝脏可能是18:3转化为22:6的重要部位。
