Diabetes and Endocrinology Research Unit, Australian National University Medical School at The Canberra Hospital, Garran, ACT, Australia.
Placenta. 2010 Mar;31(3):230-9. doi: 10.1016/j.placenta.2009.12.013. Epub 2010 Jan 20.
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 function. Trophoblasts 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 assessed. Glucose utilisation via glycolysis was near maximal at the low physiological glucose concentration of 4mM; 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 24h upregulated fatty acid esterification processes, inhibited fatty acid oxidation, inhibited glycerol release (a marker 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 TNFalpha, IL-1beta, 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 function. NEFA 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.
糖尿病妊娠的特征是母体高血糖和血脂异常，使胎盘滋养层细胞同时暴露于两者之下。目的是确定高血糖、升高的非酯化脂肪酸（NEFA）及其相互作用对滋养层细胞代谢和功能的影响。从正常足月人胎盘分离滋养层细胞，并在实验前进行 16 小时的培养。使用放射性代谢示踪剂方法，在不同的葡萄糖和 NEFA 浓度下，测定葡萄糖利用、脂肪酸氧化和脂肪酸酯化。还评估了滋养层脂质滴形成，包括脂肪细胞分化因子 mRNA 表达、活力、凋亡、合胞体化、激素和促炎细胞因子的分泌。葡萄糖通过糖酵解的利用在生理上低浓度 4mM 的葡萄糖时接近最大值；而 NEFA 酯化三酰甘油和二酰甘油随着 NEFA 浓度的增加呈线性增加，没有证据表明存在平台。将滋养层细胞在 0.25mM NEFA 中培养 24 小时，上调了脂肪酸酯化过程，抑制了脂肪酸氧化，抑制了甘油释放（脂肪分解的标志物），促进了脂肪细胞分化因子和脂质滴的形成，所有这些都与脂肪酸储存和缓冲能力的上调一致。NEFA 还促进了滋养层的合胞体化以及 TNFalpha、IL-1beta、IL-6 和 IL-10 的产生，而对细胞活力、凋亡或激素分泌没有影响。高血糖导致细胞内糖原积累和脂质滴形成减少，但对滋养层代谢或功能没有其他影响。NEFA 对滋养层代谢和功能有影响，主要与葡萄糖无关，这在糖尿病和/或肥胖症引起的妊娠中可能具有保护和病理生理作用。
