Adipogenesis is a fundamental process of white adipose tissue function, supporting lipid storage and release, while avoiding its spillover and ectopic accumulation in tissues and organs. During aging adipogenesis is impaired and among other factors, oxidative stress contributes to this process. Adipogenesis requires functional and dynamic mitochondria; however, this organelle itself becomes dysfunctional during aging and accounts for most of reactive oxygen species (ROS) production. Here, we evaluated whether oxidative stress impairs adipogenesis through functional impairment of mitodynamics by utilizing hyperoxia as a continuous source of oxidative stress while maintaining cellular viability. This negatively impacted mitochondrial function, including respiration and dynamics and ultimately blocked adipogenesis. Interestingly, this state was reversible by using the antidiabetic drug, Rosiglitazone, which reduced oxidative stress, restored mitochondrial dynamics and respiration and augmented adipogenesis. Moreover, in vitro results were in agreement with in vivo models of oxidative stress and aging, in which mice depleted of the superoxide dismutase enzyme 1 (SOD1) and old wild-type C57BL/6JRj mice demonstrated the same trend of adipogenic potential. Importantly, in humans the results follow the same pattern, showing a downregulation of adipogenic markers during aging. Since the levels of oxidative stress and peripheral insulin resistance increase with age, while adipogenesis decreases during aging, our model helps to understand a possible way to overcome physiologically low, steady stress conditions and restore adipogenesis, avoiding accumulation of deleterious hypertrophic adipocytes in favor of beneficial hyperplasia.

脂肪生成是白色脂肪组织功能的基本过程，支持脂质的存储和释放，同时避免其溢出和异位在组织和器官中的积累。在衰老过程中，脂肪形成受到损害，除其他因素外，氧化应激也促进了这一过程。脂肪生成需要功能性和动态的线粒体。然而，这种细胞器本身在衰老过程中会失灵，并占了活性氧（ROS）产生的大部分。在这里，我们评估了氧化应激是否通过利用高氧作为氧化应激的连续来源同时维持细胞生存力而通过线粒体动力学功能受损来损害脂肪生成。这会对线粒体功能（包括呼吸和动力）产生负面影响，并最终阻止脂肪形成。有趣的是 使用降糖药罗格列酮可逆转这种状态，该药可降低氧化应激，恢复线粒体动力学和呼吸作用并促进脂肪形成。此外，体外结果与体内氧化应激和衰老模型相吻合，其中耗尽超氧化物歧化酶1（SOD1）的小鼠和野生型C57BL / 6JRj小鼠表现出相同的成脂潜力。重要的是，在人类中，结果遵循相同的模式，显示出衰老过程中脂肪生成标记的下调。由于氧化应激和外周胰岛素抵抗的水平随年龄增长而增加，而衰老过程中脂肪生成减少，因此我们的模型有助于了解克服生理上低而稳定的应激条件并恢复脂肪生成的可能方法，避免有害的肥大性脂肪细胞积聚，有利于有益增生。