Saturated and unsaturated fatty acids differentially regulate in vitro and ex vivo placental antioxidant capacity

Saturated and unsaturated fatty acids differentially regulate in vitro and ex vivo placental antioxidant capacity
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DOI:
10.1111/aji.12868
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发表时间:
2018-09-01
影响因子:
3.6
通讯作者:
Reznik, Sandra E.
Reznik, Sandra E.
中科院分区:
医学3区
文献类型:
--
作者:
Manuel, Clarence R.;Charron, Maureen J.;Reznik, Sandra E.

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早产并发症是5岁以下儿童死亡的主要原因。尽管临床研究显示产妇高脂肪饮食(HFD)与早产(PTB)呈正相关,但其潜在机制仍有待阐明。此外,目前尚不清楚脂肪酸类型如何影响细菌内毒素的作用。研究方法htr -8/SVneo滋养细胞在0.5mmol(-1)棕榈酸(PA)或亚油酸(LA)中培养,不含100gmL(-1)脂多糖(LPS)或脂质胆酸(LTA)。小鼠胎盘外植体分别在2mmol (-1) PA或LA中培养,测定细胞活力、总抗氧化能力(TAC)、脂质过氧化、H2O2、血红素加氧酶-1 (HO-1)、活化B细胞核红细胞2相关因子2 (Nrf-2)和核因子-kappa轻链增强子(NF-B)转录因子活性。结果铝酸显著(i)增加细胞死亡,(ii)降低TAC, (iii)增加脂质过氧化;但HO-1无显著升高。相反,LA维持细胞活力,并显著增加TAC和HO-1。此外,用PA培养胎盘外植体可显著提高NF-B活性。与PA和LPS或LTA共孵育的细胞显著增强H2O2的产生和增加脂质过氧化。与PA和LTA共孵育的细胞协同抑制TAC, LTA比LPS更能降低TAC。与单独使用任何一种脂肪酸相比,PA/LA和LPS/LTA共孵育降低了HO-1水平。结论饱和脂肪和不饱和脂肪对胎盘活力、抗氧化能力、炎症以及革兰氏阳性和革兰氏阴性内毒素的作用有不同的调节作用。
ProblemComplications from prematurity are the leading cause of death among children under 5years of age. Although clinical studies have shown a positive correlation between maternal high-fat diet (HFD) and preterm birth (PTB), the underlying mechanisms remain to be elucidated. Furthermore, it remains unclear how fatty acid type influences the effects of bacterial endotoxins.Method of studyHTR-8/SVneo trophoblasts were cultured in either 0.5mmolL(-1) palmitic acid (PA) or linoleic acid (LA) in the absence or presence of 100gmL(-1) of lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Murine placental explants were cultured in either 2mmolL(-1) PA or LA, and cell viability, total antioxidant capacity (TAC), lipid peroxidation, H2O2, heme oxygenase-1 (HO-1), and nuclear erythroid 2-related factor 2 (Nrf-2) and nuclear factor-kappa light-chain enhancer of activated B cells (NF-B) transcription factor activity assays were assessed.ResultsPalmitic acid significantly (i) increased cell death, (ii) decreased TAC, and (iii) increased lipid peroxidation; but did not significantly increase HO-1. In contrast, LA maintained cell viability and significantly increased TAC and HO-1. In addition, incubating placental explants with PA significantly increased NF-B activity. Co-incubating cells with PA and LPS or LTA significantly potentiated H2O2 production and increased lipid peroxidation. Co-incubating cells with PA and LTA synergistically impaired TAC, and LTA decreased TAC more so than LPS. Co-incubation with PA/LA and LPS/LTA decreased HO-1 levels compared to treatment with either fatty acid alone.ConclusionOur findings suggest that saturated and unsaturated fats differentially regulate placental viability, antioxidant capacity, and inflammation and the actions of gram-positive and gram-negative endotoxins.