A Novel Function of Glycerol Kinase Alleviates LPS-Induced Inflammatory Responses by the p38/STAT3 Pathway and Mitigates ROS Generation in Kupffer Cells.

Kupffer cells (KCs), the predominant resident macrophages in the liver, exhibit an inflammatory activation state that is pathologically linked to various hepatic disorders. Studies have shown that macrophages undergo metabolic reprogramming under inflammatory conditions, and the expressions of glucose and lipid metabolism-related factors change significantly. However, glycerol kinase (GK), as a related factor that links glycolipid metabolism, the role of GK in inflammatory conditions, and its mechanism have not been reported. The aim of the present study was to explore the role of GK in the inflammatory response of KCs. LPS challenge induced marked dysregulation of glucose and lipid metabolic profiles, accompanied by a significant elevation in GK expression in pro-inflammatory KCs. GK significantly decreased the expression of pro-inflammatory factors in LPS-treated KCs. Further studies found that GK can alleviate the level of LPS-stimulated reactive oxygen species (ROS) and the expression of antioxidant factors. Meanwhile, the results showed that GK alleviates LPS-induced KCs inflammation through inhibiting the p38/STAT3 signaling pathway. The results of this study are the first to reveal that GK may alleviate Kupffer cells' inflammatory responses by inhibiting the p38/STAT3 signaling pathway and mitigating LPS-induced ROS generation. The findings provide a potential reference for future development of drugs targeting GK to prevent KCs inflammation and even liver damage.