Department of Nutrition, Exercise and Sports, Cardiovascular Physiology Group, Section of Integrative Physiology, University of Copenhagen, Copenhagen, Denmark.
Department of Biology, Section of Cell Biology and Physiology, University of Copenhagen, Copenhagen, Denmark.
Physiol Rep. 2021 Jul;9(14):e14855. doi: 10.14814/phy2.14855.
The influence of glucose and palmitic acid (PA) on mitochondrial respiration and emission of hydrogen peroxide (H O ) was determined in skeletal muscle-derived microvascular endothelial cells. Measurements were assessed in intact and permeabilized (cells treated with 0.025% saponin) low passage endothelial cells with acute-or prolonged (3 days) incubation with regular (1.7 mM) or elevated (2.2 mM) PA concentrations and regular (5 mM) or elevated (11 mM) glucose concentrations. In intact cells, acute incubation with 1.7 mM PA alone or with 1.7 mM PA + 5 mM glucose (p < .001) led to a lower mitochondrial respiration (p < 0.01) and markedly higher H O /O emission (p < 0.05) than with 5 mM glucose alone. Prolonged incubation of intact cells with 1.7 mM PA +5 mM glucose led to 34% (p < 0.05) lower respiration and 2.5-fold higher H O /O emission (p < 0.01) than incubation with 5 mM glucose alone. Prolonged incubation of intact cells with elevated glucose led to 60% lower (p < 0.05) mitochondrial respiration and 4.6-fold higher H O /O production than incubation with 5 mM glucose in intact cells (p < 0.001). All effects observed in intact cells were present also in permeabilized cells (State 2). In conclusion, our results show that acute and prolonged lipid availability, as well as prolonged hyperglycemia, induces mitochondrial dysfunction as evidenced by lower mitochondrial respiration and enhanced H O O emission. Elevated plasma substrate availability may lead to microvascular dysfunction in skeletal muscle by impairing endothelial mitochondrial function.
在骨骼肌衍生的微血管内皮细胞中，测定了葡萄糖和棕榈酸（PA）对线粒体呼吸和过氧化氢（H2O2）排放的影响。在完整和通透（用 0.025%皂素处理的细胞）的低传代内皮细胞中评估了急性或长期（3 天）孵育 1.7mM 或 2.2mM 升高的 PA 浓度以及 5mM 或 11mM 升高的葡萄糖浓度的影响。在完整的细胞中，单独用 1.7mM PA 或用 1.7mM PA+5mM 葡萄糖孵育（p<0.001）可导致线粒体呼吸降低（p<0.01），而 H2O2/O 排放显著升高（p<0.05），而单独用 5mM 葡萄糖则不然。在完整细胞中，用 1.7mM PA+5mM 葡萄糖长期孵育可导致呼吸降低 34%（p<0.05），H2O2/O 排放增加 2.5 倍（p<0.01），而单独用 5mM 葡萄糖孵育则不然。在完整细胞中，用升高的葡萄糖长期孵育可导致线粒体呼吸降低 60%（p<0.05），而与完整细胞中用 5mM 葡萄糖孵育相比，H2O2/O 生成增加 4.6 倍（p<0.001）。在通透细胞（State 2）中也存在完整细胞中观察到的所有作用。总之，我们的结果表明，急性和长期的脂质可用性以及长期高血糖会导致线粒体功能障碍，表现为线粒体呼吸降低和 H2O2 生成增加。升高的血浆底物可用性可能通过损害内皮细胞线粒体功能导致骨骼肌微血管功能障碍。
