Sanford School of Medicine, University of South Dakota, 414 E. Clark Street, Vermillion, SD 57069, USA.
Department of Pediatrics, University of Utah, 295 Chipeta Way, 2N131, Salt Lake City, UT 84108, USA.
Int J Mol Sci. 2024 Oct 27;25(21):11534. doi: 10.3390/ijms252111534.
In the parent, gestational diabetes mellitus (GDM) causes both hyperglycemia and hyperlipidemia. Despite excess lipid availability, infants exposed to GDM are at risk for essential long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Isotope studies have confirmed less LCPUFA transfer from the parent to the fetus, but how diabetic fuels impact placental fatty acid (FA) uptake and lipid droplet partitioning is not well-understood. We evaluated the effects of high glucose conditions, high lipid conditions, and their combination on trophoblast growth, viability, mitochondrial bioenergetics, BODIPY-labeled fatty acid (FA) uptake, and lipid droplet dynamics. The addition of four carbons or one double bond to FA acyl chains dramatically affected the uptake in both BeWo and primary isolated cytotrophoblasts (CTBs). The uptake was further impacted by media exposure. The combination-exposed trophoblasts had more mitochondrial protein ( = 0.01), but impaired maximal and spare respiratory capacities ( < 0.001 and < 0.0001), as well as lower viability ( = 0.004), due to apoptosis. The combination-exposed trophoblasts had unimpaired uptake of BODIPY C12 but had significantly less whole-cell and lipid droplet uptake of BODIPY C16, with an altered lipid droplet count, area, and subcellular localization, whereas these differences were not seen with individual high glucose or lipid exposure. These findings bring us closer to understanding how GDM perturbs active FA transport to increase the risk of adverse outcomes from placental and neonatal lipid accumulation alongside LCPUFA deficiency.
在母体中，妊娠糖尿病（GDM）会导致高血糖和高血脂。尽管存在过多的脂质供应，但暴露于 GDM 的婴儿仍存在必需长链多不饱和脂肪酸（LCPUFA）缺乏的风险。同位素研究已证实，LCPUFA 从母体向胎儿的转移减少，但糖尿病燃料如何影响胎盘脂肪酸（FA）摄取和脂质滴分配尚不清楚。我们评估了高葡萄糖条件、高脂条件及其组合对滋养层生长、活力、线粒体生物能学、BODIPY 标记脂肪酸（FA）摄取和脂质滴动力学的影响。在 BeWo 和原代分离的滋养细胞（CTB）中，FA 酰基链增加四个碳原子或一个双键会极大地影响摄取。培养基暴露进一步影响了摄取。由于凋亡，暴露于组合中的滋养细胞具有更多的线粒体蛋白（= 0.01），但最大和备用呼吸能力受损（< 0.001 和 < 0.0001），以及活力降低（= 0.004）。暴露于组合中的滋养细胞对 BODIPY C12 的摄取没有受损，但对 BODIPY C16 的整个细胞和脂质滴摄取明显减少，并且脂质滴计数、面积和亚细胞定位发生改变，而单独的高葡萄糖或脂质暴露则没有这些差异。这些发现使我们更接近于了解 GDM 如何扰乱主动 FA 转运，以增加胎盘和新生儿脂质积累以及 LCPUFA 缺乏的不良后果的风险。
