Effect of IL-6 and TNF-α on fatty acid uptake in cultured human primary trophoblast cells
Effect of IL-6 and TNF-α on fatty acid uptake in cultured human primary trophoblast cells
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DOI：
10.1016/j.placenta.2010.10.012
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发表时间：
2011-02-01
期刊：
影响因子：
3.8
通讯作者：
Powell, T. L.
中科院分区：
文献类型：
--
作者：
Lager, S.;Jansson, N.;Powell, T. L.
孕妇肥胖和妊娠期糖尿病(GDM)是与胎儿过度生长和胎儿过度脂肪积累相关的疾病，意味着这些妊娠中胎盘营养物质转移增加。肥胖和妊娠期糖尿病母亲的新陈代谢和激素水平发生了变化，包括母亲循环脂质和促炎细胞因子的升高。我们检验了白介素6和肿瘤坏死因子α的假说。刺激胎盘脂肪酸运输，因为这些促炎细胞因子已被证明影响其他组织的脂肪代谢。BODIPY荧光法显示，在原代培养的人滋养层细胞中，IL-6而不是肿瘤坏死因子-α刺激了脂肪酸的积累。脂肪酸积累的增加不能用胎盘脂肪酸运输中的关键成分，如脂肪酶、脂肪酸运输蛋白(FATP1)、FATP4或脂蛋白脂肪酶的表达增加来解释。在一组瘦和超重/肥胖的孕妇中，孕妇妊娠晚期血浆IL-6浓度的增加与胎盘脂蛋白脂酶活性的降低相关。然而，由于未观察到IL-6或肿瘤坏死因子-α对培养的滋养层细胞脂蛋白脂酶活性的影响，母体循环中IL-6水平与足月胎盘脂蛋白脂酶活性之间的相关性不太可能表现出因果关系。总而言之，高水平的IL-6会刺激滋养层脂肪酸的积累，这可能会在与母亲IL-6升高相关的情况下，如肥胖和妊娠期糖尿病，导致过度的营养转移。(C)2010爱思唯尔有限公司。保留所有权利。
Maternal obesity and gestational diabetes (GDM) are conditions associated with fetal overgrowth and excessive fat accumulation in the fetus, implicating an increased placental nutrient transfer in these pregnancies. Obese and GDM mothers have altered metabolism and hormone levels, including elevation of maternal circulatory lipids and pro-inflammatory cytokines. We tested the hypothesis that interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. stimulate placental fatty acid transport, as these pro-inflammatory cytokines have been shown to affect lipid metabolism in other tissues. In cultured primary human trophoblast cells IL-6, but not TNF-alpha, stimulated fatty acid accumulation, as measured by BODIPY fluorescence. The increased fatty acid accumulation could not be explained by an increased expression of key components in placental fatty acid transport, such as adipophilin, fatty acid transport protein (FATP) 1, FATP4, or lipoprotein lipase. In a cohort of lean and overweight/obese pregnant women, increasing maternal third trimester IL-6 plasma concentrations correlated with decreasing placental lipoprotein lipase activity. However, as no effect on lipoprotein lipase activity was observed in cultured trophoblast cells after exposure to either IL-6 or TNF-a, the correlation between maternal circulatory IL-6 levels and placental lipoprotein lipase activity at term is unlikely to represent a cause-and-effect relationship. In conclusion, high levels of IL-6 stimulate trophoblast fatty acid accumulation, which could contribute to an excessive nutrient transfer in conditions associated with elevated maternal IL-6 such as obesity and gestational diabetes. (C) 2010 Elsevier Ltd. All rights reserved.