Brain metabolomics and bioinformatics analyses were applied to investigate metabolic changes in a lipopolysaccharide (LPS)-induced acute inflammation mouse model. Six-week-old C57BL/6 mice received intraperitoneal LPS at 10 mg/kg to establish systemic inflammation. Control and model mice (n = 5 each) were dissected under isoflurane anesthesia, and serum, cerebrum, hippocampus, cerebellum, and hypothalamus were collected. Serum IL-1β levels were significantly elevated in the model group, confirming the establishment of systemic inflammation. Brain metabolomics revealed eight significantly altered metabolites in the cerebrum, whereas no significant changes were observed in the hippocampus, cerebellum, or hypothalamus, thereby demonstrating a region-specific effect of LPS-induced inflammation. A Random Forest model robustly differentiated model mice from control mice. Among the altered metabolites, N-acetylaspartic acid (NAA), a neuronal marker, was significantly decreased. Aspartic acid metabolism was disrupted, urea accumulated via upregulation of the urea cycle, and both aspartic acid and malic acid were reduced, suggesting an impaired function of the malate-aspartate shuttle. These findings indicate that LPS-induced systemic inflammation specifically disrupts cerebral metabolism, characterized by impairments in aspartic acid metabolism and the malate-aspartate shuttle, with NAA and urea emerging as potential biomarkers of neuroinflammation.
Sugiura et al. (2025) studied this question.