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• W2143142730 abstract "OBJECTIVE This study addressed the hypothesis that placental endothelial lipase (EL) expression is affected by pregnancies complicated by obesity and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS EL expression in placental tissues from pregnancies complicated by obesity, GDM, or obesity combined with GDM (obese-GDM) was analyzed by quantitative RT-PCR. Moreover, primary placental cells were isolated and treated with insulin, glucose, leptin, or tumor necrosis factor (TNF)-α, and EL expression was measured. Inhibitors of nuclear factor (NF)-κB or mitogen-activated protein kinase (MAPK) signaling were used to detect potential pathways of EL regulation in primary placental endothelial cells (ECs). RESULTS In placentas from obese-GDM pregnancies, EL expression was upregulated by 1.9-fold (P &lt; 0.05) compared with lean pregnancies, whereas obesity or GDM alone had no significant effect. Analyses of metabolic parameters in maternal venous and umbilical venous plasma revealed significantly increased insulin and leptin as well as slightly increased glucose and TNF-α values in the obese and obese-GDM groups. Cell culture experiments identified TNF-α and leptin, but not glucose or insulin, as regulators of EL expression in ECs. Induction of EL expression by these mediators occurred in a para/endocrine manner, since only leptin and TNF-α receptors, but not the cytokines themselves, were expressed in ECs. Inhibitor experiments suggested that TNF-α and leptin-mediated upregulation of EL may occur via two different routes. Whereas TNF-α induced EL upregulation in ECs by activation of the NF-κB pathway, leptin did not stimulate NF-κB or MAPK signaling pathways in these cells. CONCLUSIONS Metabolic inflammation with high leptin and locally increased TNF-α concentrations at the fetal-placental interface regulates placental EL expression." @default.
• W2143142730 created "2016-06-24" @default.
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• W2143142730 date "2011-09-16" @default.
• W2143142730 modified "2023-10-06" @default.
• W2143142730 title "Dysregulation of Placental Endothelial Lipase in Obese Women With Gestational Diabetes Mellitus" @default.
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• W2143142730 doi "https://doi.org/10.2337/db10-1434" @default.
• W2143142730 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3178285" @default.
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