Department of Pediatrics, Section of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO, U.S.A.
Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, U.S.A.
Clin Sci (Lond). 2018 Mar 15;132(5):595-607. doi: 10.1042/CS20171340.
Fatty acids (FA) are critical for fetal brain development and are transferred across the placenta by membrane-bound FA transport proteins (FATP), translocases (FAT/CD36), and cytosolic binding proteins (FABP). The cytosolic protein perilipin-2 aids in neutral lipid storage within lipid droplets. Decreased placental nutrient transport is believed to contribute to intrauterine growth restriction (IUGR); however, IUGR placental lipid transport and metabolism are poorly understood. We hypothesized that protein expression of FATPs, FABPs, and perilipin-2 in human placenta is decreased and placental lipid content and incorporation into lipid classes are reduced in IUGR. Placental tissue of idiopathic IUGR (=25) and gestational age-matched, appropriately grown for gestational age (AGA) fetuses (=19) was collected. We determined protein expression of FABP4 and perilipin-2 in placental homogenate and FATPs (2, 4, 6, CD36) in syncytiotrophoblast microvillous plasma membrane (MVM) by Western blot. Lipid droplet area (Oil Red O stain) and cellular FA content (GC/MS) were measured in chorionic villous tissue. MVM expression of FATP6 and CD36 was significantly increased in IUGR. The concentrations of seven -6 and -3 species long chain polyunsaturated FAs (LCPUFA) were significantly increased in the triglyceride fraction in IUGR vs AGA placenta. In summary, MVM FATP6 and CD36 protein expression is increased and LCPUFA are preferentially routed toward cellular storage in TG in the IUGR placenta, possibly to protect against oxidative stress associated with cellular FA accumulation. We speculate that these changes may be caused by impaired efflux of FA across the fetal-facing syncytiotrophoblast basal plasma membrane in IUGR placenta.
脂肪酸（FA）对于胎儿大脑发育至关重要，它们通过膜结合的 FA 转运蛋白（FATP）、转运体（FAT/CD36）和胞质结合蛋白（FABP）穿过胎盘进行转运。胞质蛋白 perilipin-2 有助于中性脂质在脂质滴中的储存。据信，胎盘营养物质转运减少会导致宫内生长受限（IUGR）；然而，IUGR 胎盘的脂质转运和代谢仍知之甚少。我们假设，人类胎盘中 FATP、FABP 和 perilipin-2 的蛋白表达减少，IUGR 胎盘的脂质含量和脂质类别掺入减少。收集特发性 IUGR（=25）和胎龄匹配、适合胎龄生长（AGA）的胎儿（=19）的胎盘组织。我们通过 Western blot 测定胎盘匀浆中 FABP4 和 perilipin-2 的蛋白表达以及合体滋养细胞微绒毛质膜（MVM）中 FATP（2、4、6、CD36）的蛋白表达。用油红 O 染色测量绒毛组织中的脂滴面积和细胞 FA 含量，并用 GC/MS 测量。IUGR 中 MVM 表达的 FATP6 和 CD36 明显增加。在 IUGR 胎盘与 AGA 胎盘相比，七种 -6 和 -3 种长链多不饱和脂肪酸（LCPUFA）的甘油三酯（TG）浓度明显增加。总之，MVM FATP6 和 CD36 的蛋白表达增加，LCPUFA 优先在 TG 中向细胞内储存，这可能是为了防止与细胞 FA 积累相关的氧化应激。我们推测，这些变化可能是由于 IUGR 胎盘中 FA 穿过面向胎儿的合体滋养细胞基底质膜的外排受损所致。
