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肥胖症及妊娠各期人胎盘脂质含量及脂质代谢酶丰度

Human placental lipid content and lipid metabolic enzyme abundance in obesity and across gestation.

机构信息

Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, U.S.A.

Department of Pediatrics, Division of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO, U.S.A.

出版信息

Clin Sci (Lond). 2022 Oct 14;136(19):1389-1404. doi: 10.1042/CS20220479.

Abstract

Changes in placental lipid metabolism influence the delivery of lipids critical for fetal development and fetal requirements for lipids change across gestation. We hypothesized that placental lipid content and metabolic enzyme protein levels increase across gestation and are elevated in obesity. Placentas (4-40 weeks' gestation) were collected from control (body mass index, BMI = 18.5-24.9, n=37) and obese (BMI > 30, n=19) pregnant women. Trophoblast villous tissue was homogenized and subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS) for phospholipid and triacylglycerol (TAG) analysis and western blot for protein quantification. The placental content of TAG species and nine of 35 identified phosphatidylcholines (PC) were significantly higher (P<0.05) in first trimester (28-79%, 10-47%, respectively). Furthermore, two TAG and three PC differed by maternal BMI and were significantly increased (P<0.05) in the obese group in first trimester (72-87%, 88-119%, respectively). Placental protein abundance of glycerol-2-phosphate (GPAT3) and 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 (AGPAT2), involved in de novo synthesis of PC and TAG, were higher (P<0.05) in the first trimester (66 and 74%, respectively). The protein abundance of the PC-remodeling enzyme PLA2G4c was also higher (63%) in first trimester (P<0.05). In conclusion, the placental content of many phospholipid and TAG species and the protein level of associated synthesis enzymes are higher in first-trimester human placenta. The high PC content may be related to the rapid membrane expansion in early pregnancy and the low placental oxygen tension may promote the accumulation of tissue TAGs in first trimester. Maternal obesity had only limited impact on placental lipid content and metabolic enzyme protein abundance.

摘要

胎盘脂质代谢的变化会影响到胎儿发育所必需的脂质的输送,而胎儿对脂质的需求在整个孕期中也会发生变化。我们假设胎盘脂质含量和代谢酶蛋白水平会随着妊娠的进展而增加,并在肥胖症中升高。我们从正常体重(BMI=18.5-24.9,n=37)和肥胖(BMI>30,n=19)孕妇的胎盘(妊娠 4-40 周)中收集了绒毛组织。将滋养层绒毛组织匀浆后,进行液相色谱串联质谱(LC-MS/MS)分析磷脂和三酰基甘油(TAG),并用 Western blot 进行蛋白定量。在妊娠早期,TAG 物质和 35 种鉴定出的磷脂酰胆碱(PC)中的 9 种的胎盘含量显著增加(P<0.05)(分别为 28-79%和 10-47%)。此外,两种 TAG 和三种 PC 的含量因母体 BMI 而异,且在妊娠早期肥胖组中显著增加(P<0.05)(分别为 72-87%和 88-119%)。胎盘甘油-2-磷酸(GPAT3)和 1-酰基-sn-甘油-3-磷酸酰基转移酶 2(AGPAT2)的蛋白丰度,这两种酶参与 PC 和 TAG 的从头合成,在妊娠早期更高(P<0.05)(分别为 66%和 74%)。PC 重塑酶 PLA2G4c 的蛋白丰度在妊娠早期也更高(63%,P<0.05)。总之,许多磷脂和 TAG 物质的胎盘含量以及相关合成酶的蛋白水平在妊娠早期的人胎盘更高。高 PC 含量可能与妊娠早期快速的膜扩张有关,而低胎盘氧分压可能促进妊娠早期组织 TAG 的积累。母体肥胖症对胎盘脂质含量和代谢酶蛋白丰度的影响有限。

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