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

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.

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.

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.

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.