J. P. Idrovo1, D. M. Boe1, R. Mcmahan1, A. TAN2, E. Kovacs1 1University Of Colorado Denver,Surgery/ Trauma Acute Care,Aurora, CO, USA 2University Of Colorado Denver,Medical Oncology/ Medicine,Aurora, CO, USA
Introduction: Elderly burn patients exhibit a lower survival rate compared with younger counterparts. The liver is highly susceptible to damage after burn injury exhibiting impaired fatty acid metabolism, which in turn worsens hepatic damage and predisposes patients to poor outcomes. β-oxidation and glutathione pathways play fundamental roles in lipid metabolism, and their derangement is associated with increased lipid peroxidation and hepatocyte injury. Herein, we explored genes and metabolites involved within these pathways from young and aged mice after burn injury.?
Methods: We compared profiles obtained from transcriptomic data, metabolomics, and quantitative polymerase chain reaction (qPCR) in liver tissue from young (4 months) and aged (20 months) mice female (BALB/c) after a 12% total body-surface-area burn. Mice were euthanized at 24 hours after injury and livers were collected.?
Results: When we compared transcriptomic data from young sham, young burn, aged sham, and aged burn mice, we identified 153 up-regulated and 229 down-regulated genes in the burn-aged group (false discovery rate <0.05 and fold change >2). The up-regulated genes in the livers from aged injured mice were associated with the innate immune response and cell death mechanisms. Notably, genes involving fatty acid and antioxidative pathways were down-regulated in livers from aged burn-injured mice while sham and young-burn animals did not show significant gene differences in similar pathways. Metabolomics analysis demonstrated a predominant reduction of beta-oxidation metabolites, including acetyl-carnitine, propionyl-carnitine, and pentanoate as well as antioxidant molecules, such as glutathione (p<0.05) in aged burn-injured mice compared with the rest of the animal groups. Glutathione peroxidase 4 (GPX4) governs antioxidant responses by regulating glutathione metabolism, qPCR data liver tissue revealed a 40% decrease in GPX4 expression (p < 0.05), comparing aged burn-injured mice with all other groups of mice.?
Conclusion: These findings suggest that beta-oxidation, as well as antioxidative metabolism, are decreased in aged mice after burn injury. Further studies will focus on the functional significance of these findings concerning hepatic homeostasis in aged injured subjects. (Supported in part by AG018859, GM115257, and 1 I01 BX004335 (EJK).)
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