Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157, Milan, Italy.
Department of Pharmacy and Biotechnology, Università di Bologna, 40127, Bologna, Italy.
Sci Rep. 2023 Sep 13;13(1):15133. doi: 10.1038/s41598-023-42333-5.
High glucose-induced endothelial dysfunction is the early event that initiates diabetes-induced vascular disease. Here we employed Cryo Soft X-ray Tomography to obtain three-dimensional maps of high D-glucose-treated endothelial cells and their controls at nanometric spatial resolution. We then correlated ultrastructural differences with metabolic rewiring. While the total mitochondrial mass does not change, high D-glucose promotes mitochondrial fragmentation, as confirmed by the modulation of fission-fusion markers, and dysfunction, as demonstrated by the drop of membrane potential, the decreased oxygen consumption and the increased production of reactive oxygen species. The 3D ultrastructural analysis also indicates the accumulation of lipid droplets in cells cultured in high D-glucose. Indeed, because of the decrease of fatty acid β-oxidation induced by high D-glucose concentration, triglycerides are esterified into fatty acids and then stored into lipid droplets. We propose that the increase of lipid droplets represents an adaptive mechanism to cope with the overload of glucose and associated oxidative stress and metabolic dysregulation.
高葡萄糖诱导的内皮功能障碍是引发糖尿病血管病变的早期事件。在这里，我们采用 Cryo 软 X 射线断层扫描技术，以纳米级空间分辨率获得高 D-葡萄糖处理的内皮细胞及其对照的三维图谱。然后，我们将超微结构差异与代谢重编程相关联。虽然总线粒体质量没有变化，但高 D-葡萄糖促进线粒体碎片化，这可以通过分裂融合标志物的调节来证实，并且功能障碍，表现为膜电位下降、耗氧量减少和活性氧产生增加。3D 超微结构分析还表明，在高 D-葡萄糖培养的细胞中积累了脂质滴。事实上，由于高 D-葡萄糖浓度诱导的脂肪酸β氧化减少，甘油三酯被酯化形成脂肪酸，然后储存到脂质滴中。我们提出，脂质滴的增加代表了一种适应机制，可以应对葡萄糖的过载以及相关的氧化应激和代谢失调。
