Wolfson STEM Centre, School of Medicine, The University of Nottingham, Nottingham, UK.
The Early Life Research Unit, Division of Child Health, Obstetrics and Gynaecology, The University of Nottingham, Nottingham, UK.
J Cell Mol Med. 2020 Oct;24(19):11434-11444. doi: 10.1111/jcmm.15749. Epub 2020 Sep 9.
Beige adipocytes possess the morphological and biochemical characteristics of brown adipocytes, including the mitochondrial uncoupling protein (UCP)1. Mesenchymal stem cells (MSCs) are somatic multipotent progenitors which differentiate into lipid-laden adipocytes. Induction of MSC adipogenesis under hypothermic culture conditions (ie 32°C) promotes the appearance of a beige adipogenic phenotype, but the stability of this phenotypic switch after cells are returned to normothermic conditions of 37°C has not been fully examined. Here, cells transferred from 32°C to 37°C retained their multilocular beige-like morphology and exhibited an intermediate gene expression profile, with both beige-like and white adipocyte characteristics while maintaining UCP1 protein expression. Metabolic profile analysis indicated that the bioenergetic status of cells initially differentiated at 32°C adapted post-transfer to 37°C, showing an increase in mitochondrial respiration and glycolysis. The ability of the transferred cells to respond under stress conditions (eg carbonyl cyanide-4-phenylhydrazone (FCCP) treatment) demonstrated higher functional capacity of enzymes involved in the electron transport chain and capability to supply substrate to the mitochondria. Overall, MSC-derived adipocytes incubated at 32°C were able to remain metabolically active and retain brown-like features after 3 weeks of acclimatization at 37°C, indicating these phenotypic characteristics acquired in response to environmental conditions are not fully reversible.
米色脂肪细胞具有棕色脂肪细胞的形态和生化特征，包括线粒体解偶联蛋白（UCP）1。间充质干细胞（MSCs）是体细胞多能祖细胞，可分化为富含脂质的脂肪细胞。在低温培养条件（即 32°C）下诱导 MSC 脂肪生成会促进米色脂肪生成表型的出现，但在将细胞恢复到 37°C 的正常温度条件后，这种表型转换的稳定性尚未得到充分研究。在这里，从 32°C 转移到 37°C 的细胞保留了它们的多腔米色样形态，并表现出中间的基因表达谱，同时具有米色样和白色脂肪细胞的特征，同时保持 UCP1 蛋白表达。代谢谱分析表明，最初在 32°C 分化的细胞在转移后适应了 37°C 的生物能量状态，表现出线粒体呼吸和糖酵解增加。在应激条件下（例如羰基氰化物-4-苯基腙（FCCP）处理），转移细胞的反应能力表明涉及电子传递链的酶的功能能力更高，并且能够向线粒体提供底物。总体而言，在 32°C 孵育的 MSC 衍生脂肪细胞在 37°C 适应 3 周后能够保持代谢活性并保留棕色样特征，这表明这些对环境条件的表型特征的获得不是完全可逆的。
