Aerobic exercise pretreatment mitigates acute lung injury through metabolic reprogramming, anti-inflammatory modulation, and 6-keto-prostaglandin F1α regulation
Year: 2025
Type: article
Abstract: OBJECTIVE: Although moderate physical exercise improves outcomes in pulmonary diseases such as acute lung injury (ALI), the underlying mechanisms, particularly those involving metabolic reprogramming, remain poorly defined. We investigated the impact of aerobic exercise (AE) pretreatment on metabolic pathways, inflammatory responses, and survival in ALI. METHODS: ALI model mice were induced through intratracheal lipopolysaccharide (LPS) after a 4-week AE protocol. Key assessments included histopathological evaluation, cytokine quantification, survival analysis, and serum metabolomic profiling. RESULTS: /NADH ratios, phosphocreatine levels, and glucose-insulin homeostasis, in addition to decreasing lactate accumulation. Metabolomic analysis identified 991 differentially expressed metabolites (DEMs) between the Con and ALI groups, predominantly enriched in metabolic pathways, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism, with arachidonic acid emerging as a critical upregulated hub node. In addition, 190 DEMs were identified between the AE + ALI and ALI groups, predominantly enriched in linoleic acid metabolism, metabolic pathways, and arachidonic acid metabolism, with linoleic acid and arachidonic acid emerging as critical upregulated hub nodes. AE pretreatment markedly suppressed the LPS-induced activation of the linoleic acid-arachidonic acid-6-keto-PGF1α signaling axis, which was aberrantly upregulated during ALI progression. Suppressing 6-keto-PGF1α activity using U51605 markedly alleviated the inflammatory response and tissue damage associated with ALI. CONCLUSIONS: AE pretreatment confers protection against ALI by orchestrating metabolic reprogramming to enhance anti-inflammatory responses. AE pretreatment attenuates LPS-induced ALI by reprogramming linoleic acid and arachidonic acid metabolism, thereby suppressing 6-keto-PGF1α biosynthesis. Pharmacological inhibition of 6-keto-PGF1α significantly alleviated ALI severity and mortality. These findings highlight AE as a preventive strategy and identify 6-keto-PGF1α as a therapeutic target for inflammatory lung injury.
Authors: Xishuai Wang, Shunqiang Nong, Qibao Zheng, Congcong Zhao, Chao Yi, Simin Li, Lunan Zhao, Xiliang Kong, Yuehui Zhou, Depeng Dong, Weina Niu, Zhuo Chen, Cong Liu, Wei Zhao, Zhuo Sun, Jie Wei, Yang Lv, Lichang Yang, Xin Jin, Shanshan Cai, Di Wu, Fugao Jiang
Institutions: Qufu Normal University, Guangzhou Medical University, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine, Qilu Institute of Technology, Sichuan University, Beijing Normal University, Northwest Normal University, Jilin University, Guangxi Medical University, First Affiliated Hospital of GuangXi Medical University, Nanjing Jiangning Hospital, Nanjing Medical University, Nanjing University of Chinese Medicine, Lancaster University, Jiangsu Province Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,240
Funders: Northwest Normal University, Qufu Normal University, Beijing Normal University, China Postdoctoral Science Foundation, Natural Science Foundation of Shandong Province, Nanjing Medical University, Science and Technology Development Plan of Shandong Province, Social Science Planning Project of Shandong Province
OpenAlex ID: W4411334624