Metabolic reprogramming consequences of sepsis: adaptations and contradictions

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.

Automated summary

The importance of cell metabolism alterations during sepsis is overlooked. Metabolic reprogramming plays a crucial role in immune imbalance and organ failure associated with sepsis. It is both necessary for immune cell activation and a cause of immunosuppression. The metabolites produced by metabolic reprogramming can control the immune response. Energy shortage in sepsis leads to cell and organ dysfunction. Metabolic reprogramming can alleviate the energy crisis and enhance cell adaptation, but switching from glycolysis to OXPHOS is essential for restoring cell function.