Metformin Modulates Systemic Lipid Remodeling after Traumatic Brain Injury
Abstract
Abstract Background Traumatic brain injury (TBI) induces systemic metabolic disturbances, particularly affecting lipid metabolism, which may contribute to secondary injury. Metformin has pleiotropic effects on mitochondrial function and lipid homeostasis, but its impact on the circulating lipidome after TBI remains poorly characterized. Methods We performed plasma lipidomic profiling in a porcine TBI model with metformin or control pretreatment. Paired pre- and post-TBI samples from 20 swine enabled within-subject comparisons. Lipidomic data were analyzed using complementary univariate and multivariate approaches, including paired differential abundance testing, principal component analysis (PCA), unsupervised hierarchical clustering with permutation-based cluster purity assessment, and sparse partial least squares discriminant analysis (sPLS-DA). Results Unsupervised analyses demonstrated coordinated lipidomic remodeling following TBI, characterized by enrichment of triglycerides and depletion of phosphatidylinositols. Metformin treatment had minimal effects on baseline metabolic profiles, with only subtle multivariate separation and near-chance classification performance. In contrast, post-TBI samples showed clearer treatment-associated differences, including improved separation in PCA, hierarchical clustering, and sPLS-DA models. These differences were driven by coordinated changes across multiple lipid classes rather than large shifts in individual metabolites. Notably,…
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