Maternal obesity is associated with a lipotoxic placental environment.
Maternal obesity is associated with a lipotoxic placental environment.
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DOI：
10.1016/j.placenta.2014.01.003
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发表时间：
2014-03
期刊：
影响因子：
3.8
通讯作者：
Shankar, K.
中科院分区：
文献类型：
--
作者：
Saben, J.;Lindsey, F.;Zhong, Y.;Thakali, K.;Badger, T. M.;Andres, A.;Gomez-Acevedo, H.;Shankar, K.
母亲肥胖与胎盘脂毒性、氧化应激和炎症有关，其中MAPK活性可能发挥核心作用。因此，我们先前已经表明，来自肥胖妇女的胎盘增加了MAPK-JNK的激活。在这里，我们对来自22名受试者的足月胎盘进行了RNA测序，这些受试者基于孕前BMI被二分为瘦型组（BMI 19-24 kg/m2; n = 12）和肥胖组（BMI，32-43 kg/m2; n = 12）。RNA-seq显示，288个基因在肥胖女性的胎盘中存在≥1.4倍的显著差异。GO分析确定了肥胖妇女胎盘中与脂质代谢、血管生成、激素活性和细胞因子活性相关的基因。表明脂毒性环境，胎盘脂质和CIDEA蛋白增加与肥胖女性胎盘中AMPK降低和NF-κB（p65）活化增加相关。此外，我们观察到肥胖女性的总抗氧化能力下降了25%，胎盘中FOXO 4核定位增加，这与JNK激活显着相关，这表明母体肥胖也可能与胎盘氧化应激增加有关。母亲肥胖也与HIF-1α蛋白表达降低相关，表明炎症/氧化应激增加与血管生成因子减少之间存在潜在联系。总之，这些发现表明，母体肥胖导致脂毒性胎盘环境，这与血管生成调节因子减少和炎症和氧化应激标志物增加有关。
Maternal obesity is associated with placental lipotoxicity, oxidative stress, and inflammation, where MAPK activity may play a central role. Accordingly, we have previously shown that placenta from obese women have increased activation of MAPK-JNK. Here, we performed RNA-sequencing on term placenta from twenty-two subjects who were dichotomized based on pre-pregnancy BMI into lean (BMI 19–24 kg/m2; n = 12) and obese groups (BMI, 32–43 kg/m2; n = 12). RNA-seq revealed 288 genes to be significantly different in placenta from obese women by ≥1.4-fold. GO analysis identified genes related to lipid metabolism, angiogenesis, hormone activity, and cytokine activity to be altered in placenta from obese women. Indicative of a lipotoxic environment, increased placental lipid and CIDEA protein were associated with decreased AMPK and increased activation of NF-κB(p65) in placenta from obese women. Furthermore, we observed a 25% decrease in total antioxidant capacity and increased nuclear FOXO4 localization in placenta from obese women that was significantly associated with JNK activation, suggesting that maternal obesity may also be associated with increased oxidative stress in placenta. Maternal obesity was also associated with decreased HIF-1α protein expression, suggesting a potential link between increased inflammation/oxidative stress and decreased angiogenic factors. Together, these findings indicate that maternal obesity leads to a lipotoxic placental environment that is associated with decreased regulators of angiogenesis and increased markers of inflammation and oxidative stress.
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