Abstract
OBJECTIVE: To investigate the temporal change patterns of energy and material metabolism in burned mice. METHODS: This study was an experimental study. Sixteen male C57BL/6N mice aged 8-10 weeks were assigned using a random number table to sham injury group (n=8) treated with sham injury and burn group (n=8) treated with burn injury. From days 1 to 14 after injury, the daily water consumption, food intake, activity level, energy expenditure, and resting energy expenditure (REE) of mice were dynamically monitored using a small animal metabolic monitoring system. Daily body weight changes and respiratory entropy from days 1 to 14 after injury, cumulative water consumption, food intake, and activity level from days 1 to 14 after injury, energy expenditure and nighttime carbohydrate and fat oxidation rates on days 1, 3, 7, 10, and 14 after injury were calculated. Forty-eight male C57BL/6N mice aged 8-10 weeks were assigned using a random number table with 8 mice being selected for sham injury, and the remaining 40 mice selected for burn injury. Cardiac blood was collected with plasma obtained from burned mice at days 1, 3, 7, 10, and 14 after injury and from sham-injured mice at 1 day after injury. Liquid chromatography-mass spectrometry was employed to identify plasma metabolites (hereinafter referred to as metabolites) and determine their temporal dynamics. Metabolites from sham-injured mice at 1 day after injury were compared with those from burned mice at the same time point, and metabolites from burned mice at days 1, 3, 7, 10, and 14 after injury were compared. Additionally, the correlation between the selected metabolites and REE was analyzed, and the relevant metabolites underwent Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. RESULTS: There were no statistically significant differences in the daily and cumulative water consumption and food intake between the sham injury group and burn group of mice from days 1 to 14 after injury (P > 0.05). Compared with those in sham injury group, the body weight changes of mice in burn group were significantly reduced from days 2 to 14 after injury (P < 0.05), the cumulative daytime and nighttime activity level were significantly reduced from days 1 to 14 after injury (P < 0.05), the daily activity level lost normal circadian rhythms from days 1 to 14 after injury, the energy expenditure was significantly reduced on day 1 (P < 0.05) but was significantly increased on days 7, 10, and 14 after injury (P < 0.05), the REE was significantly increased from days 4 to 14 after injury (P < 0.05), the respiratory entropy was significantly reduced only during nighttime from days 1 to 7 after injury (P < 0.05), the carbohydrate oxidation rates were significantly reduced at night on days 1 and 3 after injury (P < 0.05), and the fat oxidation rates were significantly increased at night on days 1, 3, and 7 after injury (P < 0.05). A total of 450 metabolites were identified in plasma samples from burned and sham-injured mice. Among these, 253 metabolites exhibited specific temporal patterns and could be clustered into 5 distinct patterns. Eighty-five metabolites of burned mice exhibited statistically significant changes following injury (P < 0.05). There were forty metabolites significantly related with REE (with variable importance in projection > 1.0), with the top metabolites including linoleic acid, oleic acid, glucose, etc. KEGG pathway enrichment analysis revealed that the biosynthesis and degradation of fatty acid, the biosynthesis and metabolism of amino acid (e.g., isoleucine and tryptophan), as well as the glycolysis/gluconeogenesis pathway were significantly associated with REE (P < 0.05). CONCLUSIONS: Both burn injury treatment and after injury time significantly affect the energy metabolism patterns and material metabolism characteristics in mice. The hypermetabolic state of burned mice persists up to 14 days after injury, during which multiple fatty acid, amino acid, and glucose metabolic pathways are associated with hypermetabolism.