Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1# Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China.
Cell Mol Life Sci. 2022 Jul 29;79(8):456. doi: 10.1007/s00018-022-04490-0.
During sepsis, the importance of alterations in cell metabolism is underappreciated. The cellular metabolism, which has a variable metabolic profile in different cells and disease stages, is largely responsible for the immune imbalance and organ failure associated with sepsis. Metabolic reprogramming, in which glycolysis replaces OXPHOS as the main energy-producing pathway, is both a requirement for immune cell activation and a cause of immunosuppression. Meanwhile, the metabolites produced by OXPHOS and glycolysis can act as signaling molecules to control the immune response during sepsis. Sepsis-induced "energy shortage" leads to stagnated cell function and even organ dysfunction. Metabolic reprogramming can alleviate the energy crisis to some extent, enhance host tolerance to maintain cell survival functions, and ultimately increase the adaptation of cells during sepsis. However, a switch from glycolysis to OXPHOS is essential for restoring cell function. This review summarized the crosstalk between metabolic reprogramming and immune cell activity as well as organ function during sepsis, discussed the benefits and drawbacks of metabolic reprogramming to show the contradictions of metabolic reprogramming during sepsis, and assessed the feasibility of treating sepsis through targeted metabolism. Using metabolic reprogramming to achieve metabolic homeostasis could be a viable therapy option for sepsis.
在脓毒症中，细胞代谢改变的重要性尚未得到充分认识。细胞代谢在不同细胞和疾病阶段具有不同的代谢特征，它在很大程度上导致了与脓毒症相关的免疫失衡和器官衰竭。代谢重编程，即糖酵解取代 OXPHOS 成为主要的能量产生途径，既是免疫细胞激活的要求，也是免疫抑制的原因。同时，OXPHOS 和糖酵解产生的代谢物可以作为信号分子，在脓毒症期间控制免疫反应。脓毒症引起的“能量短缺”导致细胞功能停滞，甚至器官功能障碍。代谢重编程在一定程度上可以缓解能量危机，增强宿主的耐受性以维持细胞存活功能，最终增加细胞在脓毒症中的适应能力。然而，从糖酵解到 OXPHOS 的转变对于恢复细胞功能至关重要。本综述总结了代谢重编程与脓毒症期间免疫细胞活性和器官功能之间的相互作用，讨论了代谢重编程的利弊，以展示脓毒症期间代谢重编程的矛盾，并评估通过靶向代谢治疗脓毒症的可行性。通过代谢重编程实现代谢平衡可能是脓毒症的一种可行治疗选择。
