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肥胖女性胎盘大血管内皮细胞中的脂肪酸转运蛋白表达及调控受损。

Fatty acid transporter expression and regulation is impaired in placental macrovascular endothelial cells in obese women.

作者信息

Yang Xiaohua, Glazebrook Patricia, Ranasinghe Geraldine C, Haghiac Maricela, Calabuig-Navarro Virtu, Minium Judi, O'Tierney-Ginn Perrie

机构信息

a Center for Reproductive Health, Metrohealth Medical Center , Case Western Reserve University School of Medicine , Cleveland , OH , USA.

出版信息

J Matern Fetal Neonatal Med. 2019 Mar;32(6):971-978. doi: 10.1080/14767058.2017.1397119. Epub 2017 Nov 5.

Abstract

OBJECTIVE

Fetal fatty acid (FA) delivery is ultimately controlled by placental transport. Focus has been the maternal-placental interface, but regulation at the feto-placental interface is unknown.

METHODS

Placental macrovascular endothelial cells (EC) (n = 4/group) and trophoblasts (TB) (n = 5/group) were isolated from lean (pregravid BMI <25 kg/m) and obese (body mass index (BMI) > 30) women. Fatty acid transporters FAT/CD36, FABPpm, FATP4, FABP 3, 4 and 5, PLIN2 and PPARα, δ, γ expression, was measured in EC and TB. Transporter response to 24 h palmitate (PA) was assessed.

RESULTS

mRNA expression of FABP3, 4, 5 and PPARγ was 2- to 3-fold reduced in EC of obese versus lean women (p < .03), but not in TB. Protein level of FABPpm was 20% lower in obese (p < .05). Palmitate (PA) up-regulated CD36, FABP3, FABP4, and PLIN2 gene expression by 3- to 4-fold in lean but not obese EC (p < .05), while PA increased FABP4 and PLIN2 in lean and obese TB, and FABP5 in lean (p < .05) EC. PA exposure up-regulated peroxisome proliferator activated receptors (PPARs) 2-fold in lean and obese EC (p < .05), but not in TB.

CONCLUSIONS

In obese women, FA transporter expression is lower in placental EC, but not TB, and less sensitive to saturated FA, compared to lean women. FA transport may be regulated at the feto-placental interface.

摘要

目的

胎儿脂肪酸(FA)的输送最终由胎盘转运控制。以往的研究重点是母胎胎盘界面,但胎儿-胎盘界面的调节机制尚不清楚。

方法

从体重正常(孕前体重指数(BMI)<25kg/m²)和肥胖(BMI>30)的孕妇中分离出胎盘大血管内皮细胞(EC)(每组n = 4)和滋养层细胞(TB)(每组n = 5)。检测EC和TB中脂肪酸转运蛋白FAT/CD36、FABPpm、FATP4、FABP 3、4和5、PLIN2以及过氧化物酶体增殖物激活受体(PPAR)α、δ、γ的表达。评估转运蛋白对24小时棕榈酸(PA)的反应。

结果

肥胖女性EC中FABP3、4、5和PPARγ 的mRNA表达比体重正常女性降低了2至3倍(p<0.03),但在TB中没有降低。肥胖女性中FABPpm的蛋白水平降低了20%(p<0.05)。棕榈酸(PA)使体重正常但非肥胖的EC中CD36、FABP3、FABP4和PLIN2基因表达上调3至4倍(p<0.05),而PA使体重正常和肥胖的TB中FABP4和PLIN2以及体重正常的EC中FABP5增加(p<0.05)。PA暴露使体重正常和肥胖EC中的过氧化物酶体增殖物激活受体(PPARs)上调2倍(p<0.05),但在TB中没有上调。

结论

与体重正常女性相比,肥胖女性胎盘EC中FA转运蛋白表达较低,但在TB中并非如此,且对饱和FA的敏感性较低。FA转运可能在胎儿-胎盘界面受到调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11d7/8459185/ee0069224ff9/nihms-1506918-f0001.jpg

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