• Han Zhong, Ri Tang, Jin-Hua Feng, Ya-Wen Peng, Qiao-Yi Xu, Yang Zhou, Zheng-Yu He, Shu-Ya Mei, and Shun-Peng Xing.
• Department of Critical Care Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
• Shock. 2024 Feb 1; 61 (2): 283293283-293.

AbstractRecent research has revealed that aerobic glycolysis has a strong correlation with sepsis-associated pulmonary fibrosis (PF). However, at present, the mechanism and pathogenesis remain unclear. We aimed to test the hypothesis that the adenosine monophosphate-activated protein kinase (AMPK) activation and suppression of hypoxia-inducible factor 1α (HIF-1α)-induced aerobic glycolysis play a central role in septic pulmonary fibrogenesis. Cellular experiments demonstrated that lipopolysaccharide increased fibroblast activation through AMPK inactivation, HIF-1α induction, alongside an augmentation of aerobic glycolysis. By contrast, the effects were reversed by AMPK activation or HIF-1α inhibition. In addition, pretreatment with metformin, which is an AMPK activator, suppresses HIF-1α expression and alleviates PF associated with sepsis, which is caused by aerobic glycolysis, in mice. Hypoxia-inducible factor 1α knockdown demonstrated similar protective effects in vivo . Our research implies that targeting AMPK activation and HIF-1α-induced aerobic glycolysis with metformin might be a practical and useful therapeutic alternative for sepsis-associated PF.Copyright © 2023 by the Shock Society.

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