Lipid Aldehydes 4-Hydroxynonenal and 4-Hydroxyhexenal Exposure Differentially Impact Lipogenic Pathways in Human Placenta.
Lipid Aldehydes 4-Hydroxynonenal and 4-Hydroxyhexenal Exposure Differentially Impact Lipogenic Pathways in Human Placenta.
复制标题
脂质醛4-羟基苯烯和4-羟基己纳尔暴露在人胎盘中差异影响脂肪生成途径。
作者：
Omega-3脂肪酸对胎儿和胎盘的最佳发育至关重要。在氧化应激的条件下，产生称为脂质醛的有毒副产物，这可能导致炎症。关于脂质醛对胎盘的影响知之甚少。我们测量了增加两种众所周知的脂质醛，4-羟基壬烯醛和4-羟基己烯醛的浓度对胎盘组织中脂质代谢基因的影响。我们发现它们对人类胎盘中脂肪酸合成和摄取途径的影响不同，这可能对氧化应激环境中omega-3脂肪酸补充剂的功效有影响。长链多不饱和脂肪酸（LCPUFA），例如欧米茄-6（n-6）花生四烯酸（AA）和n-3二十二碳六烯酸（DHA），对胎儿的正常发育和胎盘功能具有至关重要的作用。这些LCPUFA对胎儿的最佳供应对于改善出生结果和预防晚年代谢疾病的规划至关重要。虽然没有明确要求/推荐，但许多孕妇服用n-3 LCPUFA补充剂。氧化应激可导致这些LCPUFA发生脂质过氧化，产生称为脂质醛的有毒化合物。这些副产物可导致炎症状态并对组织功能产生负面影响，尽管对它们对胎盘的影响知之甚少。胎盘暴露于两种主要的脂质醛，4-羟基壬烯醛（4-HNE）和4-羟基己烯醛（4-HHE），分别由AA和DHA的过氧化反应引起，在脂质代谢的背景下进行了检查。我们评估了暴露于25 μM、50 μM和100 μM的4-HNE或4-HHE对足月人胎盘中40个脂质代谢基因的影响。4-HNE增加与脂肪生成和脂质摄取相关的基因表达（ACC、FAT 3、ACAT 1、FATP 4），4-HHE降低与脂肪生成和脂质摄取相关的基因表达（SREBP 1、SREBP 2、LDLR、SCD 1、MFSD 2a）。这些结果表明，这些脂质醛差异影响胎盘脂肪酸代谢基因在人类胎盘的表达，并可能有影响的LCPUFA补充剂在氧化应激的环境。
Omega-3 fatty acids are vital for optimal fetal and placental development. Under conditions of oxidative stress, toxic by-products called lipid aldehydes are produced, which can lead to inflammation. Little is known about the effects of lipid aldehydes on the placenta. We measured the effect of increasing the concentrations of two well-known lipid aldehydes, 4-hydroxynonenal and 4-hydroxyhexenal, on lipid metabolism genes in placental tissue. We found that they differentially impact fatty acid synthesis and uptake pathways in human placenta, which may have implications for the efficacy of omega-3 fatty acid supplementation in environments of oxidative stress. Long chain polyunsaturated fatty acids (LCPUFAs), such as the omega-6 (n-6) arachidonic acid (AA) and n-3 docosahexanoic acid (DHA), have a vital role in normal fetal development and placental function. Optimal supply of these LCPUFAs to the fetus is critical for improving birth outcomes and preventing programming of metabolic diseases in later life. Although not explicitly required/recommended, many pregnant women take n-3 LCPUFA supplements. Oxidative stress can cause these LCPUFAs to undergo lipid peroxidation, creating toxic compounds called lipid aldehydes. These by-products can lead to an inflammatory state and negatively impact tissue function, though little is known about their effects on the placenta. Placental exposure to two major lipid aldehydes, 4-hydroxynonenal (4-HNE) and 4-hydroxyhexenal (4-HHE), caused by peroxidation of the AA and DHA, respectively, was examined in the context of lipid metabolism. We assessed the impact of exposure to 25 μM, 50 μM and 100 μM of 4-HNE or 4-HHE on 40 lipid metabolism genes in full-term human placenta. 4-HNE increased gene expression associated with lipogenesis and lipid uptake (ACC, FASN, ACAT1, FATP4), and 4-HHE decreased gene expression associated with lipogenesis and lipid uptake (SREBP1, SREBP2, LDLR, SCD1, MFSD2a). These results demonstrate that these lipid aldehydes differentially affect expression of placental FA metabolism genes in the human placenta and may have implications for the impact of LCPUFA supplementation in environments of oxidative stress.
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影响因子：
9.8
作者：
Jankovic, Aleksandra;Korac, Aleksandra;Korac, Bato
通讯作者：
Korac, Bato
影响因子：
3.7
作者：
Haghiac M;Yang XH;Presley L;Smith S;Dettelback S;Minium J;Belury MA;Catalano PM;Hauguel-de Mouzon S
通讯作者：
Hauguel-de Mouzon S
影响因子：
2.1
作者：
Biri, Aydan;Bozkurt, Nuray;Durak, Ilker
通讯作者：
Durak, Ilker
影响因子：
4.6
作者：
Chen, ZH;Niki, E
通讯作者：
Niki, E
DOI：
10.1016/j.bbalip.2004.11.017
发表时间：
2005-02-21
影响因子：
4.8
作者：
Daoud, G;Simoneau, L;Lafond, J
通讯作者：
Lafond, J