Department of Public Health and Preventive Medicine, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. Institute of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Physiol Res. 2019 Dec 20;68(Suppl 3):S287-S296. doi: 10.33549/physiolres.934353.
Burden of obesity is increasing in the contemporary world. Although multifactorial in origin, appropriate mitochondrial function of adipocytes emerges as a factor essential for healthy adipocyte differentiation and adipose tissue function. Our study aimed to evaluate mitochondrial functions of human adipose-derived mesenchymal stem cells committed to adipogenesis. On days 0, 4, 10, and 21 of adipogenesis, we have characterized adipocyte proliferation and viability, quantified lipid accumulation in maturing cells, performed qualitative and quantitative analysis of mitochondria, determined mitochondrial respiration of cells using high-resolution respirometry, and evaluated mitochondrial membrane potential. In the course of adipogenesis, mitochondrial oxygen consumption progressively increased in states ROUTINE and E (capacity of the electron transfer system). State LEAK remained constant during first days of adipogenesis and then increased probably reflecting uncoupling ability of maturing adipocytes. Citrate synthase activity and volume of mitochondrial networks increased during differentiation, particularly between days 10 and 21. In addition, lipid accumulation remained low until day 10 and then significantly increased. In conclusion, during first days of adipogenesis, increased mitochondrial respiration is needed for transition of differentiating cells from glycolytic to oxidative metabolism and clonal expansion of preadipocytes and then more energy is needed to acquire typical metabolic phenotype of mature adipocyte.
肥胖的负担在当代世界不断增加。尽管肥胖的起源是多因素的，但脂肪细胞的适当线粒体功能似乎是健康脂肪细胞分化和脂肪组织功能所必需的因素。我们的研究旨在评估人类脂肪间充质干细胞向脂肪生成分化过程中的线粒体功能。在脂肪生成的第 0、4、10 和 21 天，我们对脂肪细胞的增殖和活力进行了特征分析，定量了成熟细胞中脂质的积累，对线粒体进行了定性和定量分析，使用高分辨率呼吸计测定了细胞的线粒体呼吸，并评估了线粒体膜电位。在脂肪生成过程中，线粒体耗氧量在 ROUTINE 和 E 状态（电子传递系统的能力）下逐渐增加。LEAK 状态在脂肪生成的最初几天保持不变，然后可能反映了成熟脂肪细胞的解偶联能力增加。柠檬酸合酶活性和线粒体网络体积在分化过程中增加，特别是在第 10 天和第 21 天之间。此外，脂质积累直到第 10 天才保持较低水平，然后显著增加。总之，在脂肪生成的最初几天，分化细胞从糖酵解向氧化代谢和前脂肪细胞的克隆扩张需要增加线粒体呼吸，然后需要更多的能量来获得成熟脂肪细胞的典型代谢表型。
