Fatty acids alter glycerolipid metabolism and induce lipid droplet formation, syncytialisation and cytokine production in human trophoblasts with minimal glucose effect or interaction

Fatty acids alter glycerolipid metabolism and induce lipid droplet formation, syncytialisation and cytokine production in human trophoblasts with minimal glucose effect or interaction
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DOI:
10.1016/j.placenta.2009.12.013
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发表时间:
2010-03-01
期刊:
影响因子:
3.8
通讯作者:
Nolan, C. J.
Nolan, C. J.
中科院分区:
医学3区
文献类型:
--
作者:
Pathmaperuma, A. N.;Mana, P.;Nolan, C. J.

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The diabetic pregnancy is characterized by maternal hyperglycaemia and dyslipidaemia, such that placental trophoblast cells are exposed to both The objective was to determine the effects of hyperglycaemia, elevated non-esterified fatty acids (NEFA) and their interactions on trophoblast cell metabolism and functionTrophoblasts were isolated from normal term human placentas and established in culture for 16 h prior to experiments Glucose utilisation, fatty acid oxidation and fatty acid esterification were determined using radiolabelled metabolic tracer methodology at various glucose and NEFA concentrations Trophoblast lipid droplet formation including adipophilin mRNA expression, viability, apoptosis, syncytialisation, secretion of hormones and pro-inflammatory cytokines were also assessedGlucose utilisation via glycolysis was near maximal at the low physiological glucose concentration of 4 mM, whereas NEFA esterification into triacylglycerol and diacylglycerol increased linearly with increasing NEFA concentrations without evidence of plateau Culture of trophoblasts in 0 25 mM NEFA for 24 h upregulated fatty acid esterification processes, inhibited fatty acid oxidation, inhibited glycerol release (a market of lipolysis) and promoted adipophilin and lipid droplet formation, all consistent with upregulation of fatty acid storage and buffering capacity. NEFA also promoted trophoblast syncytialisation and TNF alpha, IL-1 beta, IL-6 and IL-10 production without effects on cell viability. apoptosis or hormone secretion Hyperglycaemia caused intracellular glycogen accumulation and reduced lipid droplet formation, but had no other effects on trophoblast metabolism or functionNEFA have effects on trophoblast metabolism and function, mostly independent of glucose, that may have protective as well as pathophysiological roles in pregnancies complicated by diabetes and/or obesity. (C) 2009 Elsevier Ltd All rights reserved.