Lipidomic profiling reveals time-resolved oxylipin responses to severe burn injury

BACKGROUND: Severe burn injuries affecting more than 40% of the total body surface area (TBSA) are associated with a high risk of mortality. Clinically, burn injury is accompanied by increased systemic inflammation, adipose tissue lipolysis, and skeletal muscle catabolism that can contribute to muscle wasting. Despite the well-established role of inflammation in mediating these processes, the role of circulating oxylipins, released from various tissues and potentially linked to the inflammatory response, remains poorly understood. METHODS: In this study, we investigated the temporal dynamics of plasma oxylipins in male and female patients with severe burn injuries (n = 7, mean TBSA 61 ± 6%) over a 33-day period post-injury, using high-resolution lipidomic profiling. A total of 114 lipid species were quantified, revealing distinct time-dependent alterations in both pro-inflammatory and anti-inflammatory lipid mediators. In addition, selected oxylipins were evaluated in C2C12 myotubes to test whether they engage atrophy-related and inflammatory transcriptional programs. RESULTS: Specifically, levels of the pro-inflammatory oxylipins 15-hydroxyeicosatetraenoic acid (15-HETE) and its downstream metabolite 15-oxo-eicosatetraenoic acid (15-oxoETE) were elevated immediately after injury, whereas the anti-inflammatory oxylipin resolvin D1 (RvD1) peaked during the later phase of recovery. C2C12 myotubes incubated with 15-oxoETE increased expression of genes involved in muscle protein catabolism and inflammation, while co-incubation with RvD1 attenuated this transcriptional response. CONCLUSION: These findings define dynamic changes in the plasma lipidome following severe burn injury and identify selected burn-regulated oxylipins that can modulate skeletal muscle stress- and catabolism-related transcriptional programs in vitro.